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CHAPTER 18
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The Endocrine System

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The Endocrine System and Homeostasis

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The hormones of the endocrine system contribute to homeostasis by regulating the activity and
growth of target cells in your body. Hormones also regulate your metabolism.
As girls and boys enter puberty, they start to develop striking differences homeostasis on a daily basis. They regulate the activity of smooth
in physical appearance and behavior. Perhaps no other period in life muscle, cardiac muscle, and some glands; alter metabolism; spur growth
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so dramatically shows the impact of the endocrine system in directing and development; influence reproductive processes; and participate in
development and regulating body functions. In girls, estrogens promote circadian (daily) rhythms established by the suprachiasmatic nucleus of
accumulation of adipose tissue in the breasts and hips, sculpting a the hypothalamus.
feminine shape. At the same time or a little later, increasing levels of
testosterone in boys begin to help build muscle mass and enlarge the
vocal cords, producing a lower-pitched voice. These changes are just
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a few examples of the powerful influence of endocrine secretions. Q Did you ever wonder why thyroid gland disorders affect all
Less dramatically, perhaps, multitudes of hormones help maintain major body systems?
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18.2 Endocrine Glands 623
glands and hormone-producing tissues and examine how their hor-

18.1 Comparison of Control mones govern body activities.
by the Nervous and

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Endocrine Systems Checkpoint

1. List the similarities among and differences between the nervous and
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endocrine systems with regard to the control of homeostasis.
OBJECTIVE
• Compare control of body functions by the nervous system and

endocrine system.
18.2 Endocrine Glands
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The nervous and endocrine systems act together to coordinate functions

of all body systems. Recall that the nervous system acts through nerve OBJECTIVE
impulses (action potentials) conducted along axons of neurons. At
synapses, nerve impulses trigger the release of mediator (messenger) • Distinguish between exocrine and endocrine glands.
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molecules called neurotransmitters (shown in Figure 12.23). The endo-
crine system also controls body activities by releasing mediators, called
hormones, but the means of control of the two systems are very different. Recall from Chapter 4 that the body contains two kinds of glands:
A hormone (hormon = to excite or get moving) is a molecule that exocrine glands and endocrine glands. Exocrine glands (EKS-ō-
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is released in one part of the body but regulates the activity of cells in krin; exo- = outside) secrete their products into ducts that carry the
other parts of the body. Most hormones enter interstitial fluid and secretions into body cavities, into the lumen of an organ, or to the
then the bloodstream. The circulating blood delivers hormones to outer surface of the body. Exocrine glands include sudoriferous
cells throughout the body. Both neurotransmitters and hormones ex- (sweat), sebaceous (oil), mucous, and digestive glands. Endocrine
ert their effects by binding to receptors on or in their “target” cells. glands (EN-dō-krin; endo- = within) secrete their products (hor-
Several chemicals act as both neurotransmitters and hormones. One mones) into the interstitial fluid surrounding the secretory cells
familiar example is norepinephrine, which is released as a neuro- rather than into ducts. From the interstitial fluid, hormones diffuse
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transmitter by sympathetic postganglionic neurons and as a hormone into blood capillaries and blood carries them to target cells through-
by chromaffin cells of the adrenal medullae. out the body. Because of their dependence on the cardiovascular
Responses of the endocrine system often are slower than re- system to distribute their products, endocrine glands are some of
sponses of the nervous system; although some hormones act within the most vascular tissues of the body. Considering that most hor-
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seconds, most take several minutes or more to cause a response. The mones are required in very small amounts, circulating levels typi-
effects of nervous system activation are generally briefer than those cally are low.
of the endocrine system. The nervous system acts on specific muscles The endocrine glands include the pituitary, thyroid, parathyroid,
and glands. The influence of the endocrine system is much broader; it adrenal, and pineal glands (Figure 18.1). In addition, several organs
helps regulate virtually all types of body cells. and tissues are not exclusively classified as endocrine glands but
We will also have several opportunities to see how the nervous contain cells that secrete hormones. These include the hypothalamus,
y,
and endocrine systems function together as an interlocking “super- thymus, pancreas, ovaries, testes, kidneys, stomach, liver, small intestine,
system.” For example, certain parts of the nervous system stimulate skin, heart, adipose tissue, and placenta. Taken together, all endocrine
or inhibit the release of hormones by the endocrine system. glands and hormone-secreting cells constitute the endocrine system
Table 18.1 compares the characteristics of the nervous and (EN′-dō-krin; endo- = within; -crino = to secrete). The science of the
endocrine systems. In this chapter, we focus on the major endocrine structure and function of the endocrine glands and the diagnosis and
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TA B LE 1 8 . 1 Comparison of Control by the Nervous and Endocrine Systems
CHARACTERISTIC NERVOUS SYSTEM ENDOCRINE SYSTEM

Molecules Neurotransmitters released locally in response Hormones delivered to tissues throughout body by
to nerve impulses. blood.
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Site of action Close to site of release, at synapse; binds to receptors Far from site of release (usually); binds to receptors on
in postsynaptic membrane. or in target cells.
Types of target cells Muscle (smooth, cardiac, and skeletal) cells, gland cells, Cells throughout body.
other neurons.
Time to onset of action Typically within milliseconds (thousandths of a second). Seconds to hours or days.
Duration of action Generally briefer (milliseconds). Generally longer (seconds to days).
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624 CH A PT E R 18 The Endocrine System
FIGURE 18.1 Location of many endocrine glands. Also shown are other Functions of Hormones • Glandular secretions.
organs that contain endocrine cells and associated structures. 1. Help regulate: • Some immune system activities.
• Chemical composition and 2. Control growth and
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Endocrine glands secrete hormones, which circulating blood delivers to volume of internal environment development.
target tissues. (extracellular fluid). 3. Regulate operation of
• Metabolism and energy balance. reproductive systems.
• Contraction of smooth and
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4. Help establish circadian rhythms.
cardiac muscle fibers.
Pineal gland
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Hypothalamus
Thyroid Pituitary
Gland Parathyroid gland
glands (behind
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thyroid glands)
Trachea
Thyroid gland
Trachea
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Skin
Thymus
Lung
Heart
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Liver Stomach
Kidney
Adrenal
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glands
Uterus
Pancreas
Small
intestine Ovary
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Female
Scrotum
Testes
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Male
Q What is the basic difference between endocrine glands and exocrine glands?
treatment of disorders of the endocrine system is known as endocri-

18.3 Hormone Activity
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nology (-logy = study of).
OBJECTIVES
Checkpoint
2. List three organs or tissues that are not exclusively classified as
• Describe how hormones interact with target-cell receptors.
endocrine glands but contain cells that secrete hormones. • Compare the two chemical classes of hormones based on their solubility.
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18.3 Hormone Activity 625
The Role of Hormone Receptors FIGURE 18.2 Comparison between circulating hormones and local
hormones (autocrines and paracrines).
Although a given hormone travels throughout the body in the blood,
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it affects only specific target cells. Hormones, like neurotransmitters, Circulating hormones are carried through the bloodstream to act on
distant target cells. Paracrines act on neighboring cells, and autocrines
influence their target cells by chemically binding to specific
act on the same cells that produced them.
protein receptors. Only the target cells for a given hormone have
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receptors that bind and recognize that hormone. For example,
thyroid-stimulating hormone (TSH) binds to receptors on cells of the Endocrine
thyroid gland, but it does not bind to cells of the ovaries because cell
Blood
ovarian cells do not have TSH receptors. capillary
Circulating
Receptors, like other cellular proteins, are constantly being hormone
synthesized and broken down. Generally, a target cell has 2000 to
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100,000 receptors for a particular hormone. If a hormone is present in
excess, the number of target-cell receptors may decrease—an effect
called down-regulation. For example, when certain cells of the testes Hormone
are exposed to a high concentration of luteinizing hormone (LH), the receptor
number of LH receptors decreases. Down-regulation makes a
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target cell less sensitive to a hormone. In contrast, when a hormone
is deficient, the number of receptors may increase. This phenom- Distant target cells
enon, known as up-regulation, makes a target cell more sensitive
(a) Circulating hormones
to a hormone.
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Clinical Connection Paracrine receptor
Blocking Hormone Receptors

Paracrine
Synthetic hormones that block the receptors for some naturally occur- Paracrine cell Nearby target cell
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ring hormones are available as drugs. For example, RU486 (mifepristone),
which is used to induce abortion, binds to the receptors for progesterone (a Autocrine
female sex hormone) and prevents progesterone from exerting its normal receptor
effect, in this case preparing the lining of the uterus for implantation. When Autocrine
RU486 is given to a pregnant woman, the uterine conditions needed for cell
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nurturing an embryo are not maintained, embryonic development stops,
and the embryo is sloughed off along with the uterine lining. This example Autocrine
illustrates an important endocrine principle: If a hormone is prevented
from interacting with its receptors, the hormone cannot perform its nor- (b) Local hormones (paracrines and autocrines)
mal functions.
Q In the stomach, one stimulus for secretion of hydrochloric
y,
acid by parietal cells is the release of histamine by
neighboring mast cells. Is histamine an autocrine or a
paracrine in this situation?
Circulating and Local Hormones
Most endocrine hormones are circulating hormones—they pass
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from the secretory cells that make them into interstitial fluid and secrete even more IL-2 and thus strengthen the immune response.
then into the blood (Figure 18.2a). Other hormones, termed local Another example of a local hormone is the gas nitric oxide (NO),
hormones, act locally on neighboring cells or on the same cell that which is released by endothelial cells lining blood vessels. NO
secreted them without entering the bloodstream (Figure 18.2b). causes relaxation of nearby smooth muscle fibers in blood vessels,
Local hormones that act on neighboring cells are called parac- which in turn causes vasodilation (increase in blood vessel
rines (PAR-a-krins; para- = beside or near), and those that act on diameter). The effects of such vasodilation range from a lowering
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the same cell that secreted them are called autocrines (AW-tō- of blood pressure to erection of the penis in males. The drug
krins; auto- = self). One example of a local hormone is interleu- Viagra® (sildenafil) enhances the effects stimulated by nitric oxide
kin-2 (IL-2), which is released by helper T cells (a type of white in the penis.
blood cell) during immune responses (see Chapter 22). IL-2 helps Local hormones usually are inactivated quickly; circulating hor-
activate other nearby immune cells, a paracrine effect. But it also mones may linger in the blood and exert their effects for a few min-
acts as an autocrine by stimulating the same cell that released it to utes or occasionally for a few hours. In time, circulating hormones
proliferate. This action generates more helper T cells that can are inactivated by the liver and excreted by the kidneys. In cases of
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kidney or liver failure, excessive levels of hormones may build up in Hormone Transport in the Blood
the blood.
Most water-soluble hormone molecules circulate in the watery blood
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plasma in a “free” form (not attached to other molecules), but most
Chemical Classes of Hormones lipid-soluble hormone molecules are bound to transport proteins.
Chemically, hormones can be divided into two broad classes: those The transport proteins, which are synthesized by cells in the liver,
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that are soluble in lipids, and those that are soluble in water. This have three functions:
chemical classification is also useful functionally because the two
1. They make lipid-soluble hormones temporarily water-soluble, thus
classes exert their effects differently.
increasing their solubility in blood.
Lipid-Soluble Hormones The lipid-soluble hormones 2. They retard passage of small hormone molecules through the filter-
include steroid hormones, thyroid hormones, and nitric oxide. ing mechanism in the kidneys, thus slowing the rate of hormone
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loss in the urine.
1. Steroid hormones are derived from cholesterol. Each steroid 3. They provide a ready reserve of hormone, already present in the
hormone is unique due to the presence of different chemical groups bloodstream.
attached at various sites on the four rings at the core of its structure
(see Table 18.2). These small differences allow for a large diversity In general, 0.1–10% of the molecules of a lipid-soluble hormone
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of functions. are not bound to a transport protein. This free fraction diffuses
2. Two thyroid hormones (T3 and T4) are synthesized by attaching out of capillaries, binds to receptors, and triggers responses. As
iodine to the amino acid tyrosine. The presence of two benzene free hormone molecules leave the blood and bind to their receptors,
rings within a T3 or T4 molecule makes these molecules very transport proteins release new ones to replenish the free fraction.
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lipid-soluble (see Table 18.2).
3. The gas nitric oxide (NO) is both a hormone and a neurotrans- Clinical Connection
mitter. Its synthesis is catalyzed by the enzyme nitric oxide
synthase. Administering Hormones
Both steroid hormones and thyroid hormones are effective when taken by
Water-Soluble Hormones The water-soluble hormones mouth. They are not split apart during digestion and easily cross the in-
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include amine hormones, peptide and protein hormones, and testinal lining because they are lipid-soluble. By contrast, peptide and pro-
eicosanoid hormones. tein hormones, such as insulin, are not effective oral medications because
- digestive enzymes destroy them by breaking their peptide bonds. This is
1. Amine hormones (a-MEN) are synthesized by decarboxylating
why people who need insulin must take it by injection.
(removing a molecule of CO2) and otherwise modifying certain
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amino acids. They are called amines because they retain an amino
group ( NH3+). The catecholamines—epinephrine, norepineph-
rine, and dopamine—are synthesized by modifying the amino acid Checkpoint
tyrosine. Histamine is synthesized from the amino acid histidine by
mast cells and platelets. Serotonin and melatonin are derived 3. What is the difference between down-regulation and up-regulation?
from tryptophan. 4. Identify the chemical classes of hormones, and give an example of each.
y,
2. Peptide hormones and protein hormones are amino acid 5. How are hormones transported in the blood?
polymers. The smaller peptide hormones consist of chains of 3 to
49 amino acids; the larger protein hormones include 50 to 200
amino acids. Examples of peptide hormones are antidiuretic
hormone and oxytocin; protein hormones include growth
hormone and insulin. Several of the protein hormones, such
18.4 Mechanisms of Hormone
20
as thyroid-stimulating hormone, have attached carbohydrate Action
groups and thus are glycoprotein hormones.
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3. The eicosanoid hormones (ī-KO-sa-noyd; eicos- = twenty forms; OBJECTIVE
-oid = resembling) are derived from arachidonic acid, a 20-carbon • Describe the two general mechanisms of hormone action.
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fatty acid. The two major types of eicosanoids are prostaglandins
(PGs) and leukotrienes (LTs). The eicosanoids are important local
hormones, and they may act as circulating hormones as well. The response to a hormone depends on both the hormone itself and
Table 18.2 summarizes the classes of lipid-soluble and water- the target cell. Various target cells respond differently to the same
soluble hormones and provides an overview of the major hormones hormone. Insulin, for example, stimulates synthesis of glycogen in
and their sites of secretion. liver cells and synthesis of triglycerides in adipose cells.
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18.4 Mechanisms of Hormone Action 627
TA B LE 1 8 . 2 Summary of Hormones by Chemical Class
CHEMICAL CLASS HORMONES SITE OF SECRETION

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LIPID-SOLUBLE
Steroid hormones Aldosterone, cortisol, androgens. Adrenal cortex.
O CH2OH Calcitriol (active form of vitamin D). Kidneys.

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C O Testosterone. Testes.
H C
HO Estrogens, progesterone. Ovaries.
H3C
Aldosterone
O
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Thyroid hormones T3 (triiodothyronine), T4 (thyroxine). Thyroid gland (follicular cells).
H H
HO O C C COOH
H NH2
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Triiodothyronine (T3)
Gas Nitric oxide (NO). Endothelial cells lining blood vessels.

WATER-SOLUBLE
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Amines Epinephrine, norepinephrine (catecholamines). Adrenal medulla.
CH CH2 NH2 Melatonin. Pineal gland.
OH Histamine. Mast cells in connective tissues.
Serotonin. Platelets in blood.
HO
OH Norepinephrine
Peptides and proteins All hypothalamic releasing and inhibiting hormones. Hypothalamus.
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Glutamine Isoleucine Oxytocin, antidiuretic hormone. Posterior pituitary.
Asparagine Tyrosine
Growth hormone, thyroid-stimulating hormone, Anterior pituitary.
adrenocorticotropic hormone, follicle-stimulating
Cysteine S S Cysteine hormone, luteinizing hormone, prolactin, melanocyte-
stimulating hormone.
Proline
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Insulin, glucagon, somatostatin, pancreatic polypeptide. Pancreas.
Leucine
Parathyroid hormone. Parathyroid glands.
Glycine Oxytocin Calcitonin. Thyroid gland (parafollicular cells).
NH2 Gastrin, secretin, cholecystokinin, GIP (glucose- Stomach and small intestine (enteroendocrine
dependent insulinotropic peptide). cells).
Erythropoietin. Kidneys.
y,
Leptin. Adipose tissue.
Eicosanoids Prostaglandins, leukotrienes. All cells except red blood cells.
HO
COOH
OH
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A leukotriene (LTB4)
The response to a hormone is not always the synthesis of new lipid-soluble hormones are located inside target cells. The receptors
molecules, as is the case for insulin. Other hormonal effects include for water-soluble hormones are part of the plasma membrane of
changing the permeability of the plasma membrane, stimulating target cells.
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transport of a substance into or out of the target cells, altering the rate
of specific metabolic reactions, or causing contraction of smooth Action of Lipid-Soluble Hormones
muscle or cardiac muscle. In part, these varied effects of hormones are
possible because a single hormone can set in motion several different As you just learned, lipid-soluble hormones, including steroid hor-
cellular responses. However, a hormone must first “announce its mones and thyroid hormones, bind to receptors within target cells.
arrival” to a target cell by binding to its receptors. The receptors for Their mechanism of action is as follows (Figure 18.3):
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FIGURE 18.3 Mechanism of action of the lipid-soluble steroid known as cyclic AMP (cAMP). Neurotransmitters, neuropeptides,
hormones and thyroid hormones. and several sensory transduction mechanisms (for example, vision;
see Figure 17.16) also act via second-messenger systems.
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Lipid-soluble hormones bind to receptors inside target cells. The action of a typical water-soluble hormone occurs as follows
(Figure 18.4):
Free hormone Blood capillary
1 A water-soluble hormone (the first messenger) diffuses from the
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blood through interstitial fluid and then binds to its receptor
1 Lipid-soluble at the exterior surface of a target cell’s plasma membrane. The
Transport hormone
protein diffuses into cell
hormone–receptor complex activates a membrane protein called
a G protein. The activated G protein in turn activates adenylyl
-
cyclase (a-DEN-i-lil SI -klās).
2 Activated Nucleus 2 Adenylyl cyclase converts ATP into cyclic AMP (cAMP). Because
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receptor–hormone
Receptor
complex alters the enzyme’s active site is on the inner surface of the plasma
gene expression
membrane, this reaction occurs in the cytosol of the cell.
DNA
Cytosol FIGURE 18.4 Mechanism of action of the water-soluble hormones
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mRNA (amines, peptides, proteins, and eicosanoids).
3 Newly formed
mRNA directs Ribosome
synthesis of Water-soluble hormones bind to receptors embedded in the plasma
specific proteins New membranes of target cells.
on ribosomes protein
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4 New proteins alter Blood capillary
cell's activity
Target cell
Q What is the action of the receptor–hormone complex? 1 Binding of hormone (first messenger)
Water-soluble to its receptor activates G protein,
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hormone which activates adenylyl cyclase
1 A free lipid-soluble hormone molecule diffuses from the blood, Receptor Adenylyl cyclase
through interstitial fluid, and through the lipid bilayer of the
plasma membrane into a cell. Second messenger
G protein
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2 If the cell is a target cell, the hormone binds to and activates ATP 2 Activated adenylyl
cAMP
receptors located within the cytosol or nucleus. The activated cyclase converts
ATP to cAMP
receptor–hormone complex then alters gene expression: It turns
specific genes of the nuclear DNA on or off. Protein kinases 6 Phosphodiesterase
inactivates cAMP
3 As the DNA is transcribed, new messenger RNA (mRNA) forms, 3 cAMP serves as a Activated
leaves the nucleus, and enters the cytosol. There, it directs second messenger protein
y,
to activate protein kinases
synthesis of a new protein, often an enzyme, on the ribosomes. kinases
4 The new proteins alter the cell’s activity and cause the responses 4 Activated protein
Protein kinases
typical of that hormone. phosphorylate
ATP cellular proteins
Action of Water-Soluble Hormones

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ADP
Because amine, peptide, protein, and eicosanoid hormones are not
lipid-soluble, they cannot diffuse through the lipid bilayer of the
Protein – P
plasma membrane and bind to receptors inside target cells. Instead,
water-soluble hormones bind to receptors that protrude from 5 Millions of phosphorylated
the target-cell surface. The receptors are integral transmembrane proteins cause reactions that
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proteins in the plasma membrane. When a water-soluble hormone produce physiological responses
binds to its receptor at the outer surface of the plasma membrane, it
acts as the first messenger. The first messenger (the hormone) then
causes production of a second messenger inside the cell, where
Target cell
specific hormone-stimulated responses take place. One common
second messenger is cyclic adenosine monophosphate, also Q Why is cAMP a “second messenger”?
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18.5 Control of Hormone Secretion 629
3 Cyclic AMP (the second messenger) activates one or more protein Hormone Interactions
kinases, which may be free in the cytosol or bound to the plasma
membrane. A protein kinase is an enzyme that phosphorylates (adds The responsiveness of a target cell to a hormone depends on (1) the
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a phosphate group to) other cellular proteins (such as enzymes). The hormone’s concentration in the blood, (2) the abundance of the target
donor of the phosphate group is ATP, which is converted to ADP. cell’s hormone receptors, and (3) influences exerted by other hor-
4 Activated protein kinases phosphorylate one or more cellular mones. A target cell responds more vigorously when the level of a hor-
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proteins. Phosphorylation activates some of these proteins and mone rises or when it has more receptors (up-regulation). In addition,
inactivates others, rather like turning a switch on or off. the actions of some hormones on target cells require a simultaneous
or recent exposure to a second hormone. In such cases, the second
5 Phosphorylated proteins in turn cause reactions that produce
hormone is said to have a permissive effect. For example, epineph-
physiological responses. Different protein kinases exist within
rine alone only weakly stimulates lipolysis (the breakdown of triglyc-
different target cells and within different organelles of the same
erides), but when small amounts of thyroid hormones (T3 and T4) are
target cell. Thus, one protein kinase might trigger glycogen synthesis,
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present, the same amount of epinephrine stimulates lipolysis much
a second might cause the breakdown of triglyceride, a third may
more powerfully. Sometimes the permissive hormone increases the
promote protein synthesis, and so forth. As noted in step 4 ,
number of receptors for the other hormone, and sometimes it pro-
phosphorylation by a protein kinase can also inhibit certain proteins.
motes the synthesis of an enzyme required for the expression of the
For example, some of the kinases unleashed when epinephrine binds
other hormone’s effects.
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to liver cells inactivate an enzyme needed for glycogen synthesis.
When the effect of two hormones acting together is greater than
6 After a brief period, an enzyme called phosphodiesterase
the sum of their individual effects, the two hormones are said to have a
(fos′-fō-dī-ES-ter′-ās) inactivates cAMP. Thus, the cell’s response
synergistic effect. For example, both glucagon and epinephrine in-
is turned off unless new hormone molecules continue to bind to
crease the blood glucose concentration by stimulating the breakdown
their receptors in the plasma membrane.
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of glycogen in liver cells. When both hormones are present, the increase
in blood glucose concentration is greater than the sum of the individual
The binding of a hormone to its receptor activates many G-protein
hormone responses. Synergistic effects are thought to occur because
molecules, which in turn activate molecules of adenylyl cyclase (as
the hormones activate pathways that lead to formation of the same
noted in step 1 ). Unless they are further stimulated by the binding of
types of second messengers, thereby amplifying the cellular response.
more hormone molecules to receptors, G proteins slowly inactivate,
When one hormone opposes the actions of another hormone,
thus decreasing the activity of adenylyl cyclase and helping to stop
the two hormones are said to have antagonistic effects. An example
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the hormone response. G proteins are a common feature of most sec-
of a pair of hormones with antagonistic effects is insulin and
ond-messenger systems.
glucagon: Insulin promotes synthesis of glycogen by liver cells, and
Many hormones exert at least some of their physiological effects
glucagon stimulates breakdown of glycogen in the liver. Antagonistic
through the increased synthesis of cAMP. Examples include antidiuretic
effects occur because the hormones activate pathways that cause
hormone (ADH), thyroid-stimulating hormone (TSH), adrenocortico-
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opposite cellular responses or one hormone decreases the number of
tropic hormone (ACTH), glucagon, epinephrine, and hypothalamic re-
receptors (down-regulation) for the other hormone.
leasing hormones. In other cases, such as growth hormone–inhibiting
hormone (GHIH), the level of cyclic AMP decreases in response to the
binding of a hormone to its receptor. Besides cAMP, other second
Checkpoint
messengers include calcium ions (Ca2+); cyclic guanosine monophos- 6. What factors determine the responsiveness of a target cell
y,
phate, also referred to as cyclic GMP (cGMP), a cyclic nucleotide to a hormone?
-
similar to cAMP; inositol trisphosphate (IP3) (in-O-si-tōl tris-FOS-fāt);
7. What are the differences among permissive effects, synergistic
and diacylglycerol (DAG) (dī′-as-il-GLIS-er-ol). A given hormone may effects, and antagonistic effects of hormones?
use different second messengers in different target cells.
Hormones that bind to plasma membrane receptors can induce
their effects at very low concentrations because they initiate a cas-
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cade or chain reaction, each step of which multiplies or amplifies
the initial effect. For example, the binding of a single molecule of
18.5 Control of Hormone
epinephrine to its receptor on a liver cell may activate a hundred or
so G proteins, each of which activates an adenylyl cyclase molecule.
Secretion
If each adenylyl cyclase produces even 1000 cAMP, then 100,000 of
these second messengers will be liberated inside the cell. Each cAMP OBJECTIVE
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may activate a protein kinase, which in turn can act on hundreds or
thousands of substrate molecules. Some of the kinases phosphoryl- • Describe the mechanisms of control of hormone secretion.
ate and activate a key enzyme needed for glycogen breakdown. The
end result of the binding of a single molecule of epinephrine to its
receptor is the breakdown of millions of glycogen molecules into Control of hormone secretion. The release of most hormones occurs
glucose monomers. in short bursts, with little or no secretion between bursts. When
stimulated, an endocrine gland will
596
release its hormone in more frequent bursts, increasing the concen- by a stalk, the infundibulum (in-fun-DIB-ū-lum = a funnel; Figure
tration of the hormone in the blood. In the absence of stimulation, the 18.5a), and has two anatomically and functionally separate por-
blood level of the hormone decreases. Regulation of secretion nor- tions: the anterior pituitary and the posterior pituitary. The anteri-
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mally prevents overproduction or underproduction of any given hor- or pituitary (anterior lobe), also called the adenohypophysis (ad′-e-
mone to help maintain homeostasis. nō-hī-POF-i-sis; adeno- = gland; -hypophysis = undergrowth),
Hormone secretion is regulated by (1) signals from the nervous accounts for about 75% of the total weight of the gland and is com-
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system, (2) chemical changes in the blood, and (3) other hormones. posed of epithelial tissue. The anterior pituitary consists of two
For example, nerve impulses to the adrenal medullae regulate the parts in an adult: The pars distalis is the larger portion, and the
release of epinephrine; blood Ca2+ level regulates the secretion of pars tuberalis (PARS too-be′-RAL-is) forms a sheath around the in-
parathyroid hormone; and a hormone from the anterior pituitary fundibulum. The posterior pituitary (posterior lobe), also called
(adrenocorticotropic hormone) stimulates the release of cortisol by the neurohypophysis (noo′-rō-hī-POF-i-sis; neuro- = nerve), is com-
the adrenal cortex. Most hormonal regulatory systems work via neg- posed of neural tissue. It also consists of two parts: the pars ner-
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ative feedback (see Figure 1.4), but a few operate via positive feed- -
vosa (ner-VO-sa), the larger bulbar portion, and the infundibulum.
back (see Figure 1.5). For example, during childbirth, the hormone A third region of the pituitary gland called the pars intermedia at-
oxytocin stimulates contractions of the uterus, and uterine contrac- rophies during human fetal development and ceases to exist as a
tions in turn stimulate more oxytocin release, a positive feedback separate lobe in adults (see Figure 18.20b). However, some of its
effect. cells migrate into adjacent parts of the anterior pituitary, where
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Now that you have a general understanding of the roles of hor- they persist.
mones in the endocrine system, we turn to discussions of the various
endocrine glands and the hormones they secrete.
Anterior Pituitary
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The anterior pituitary secretes hormones that regulate a wide range

Checkpoint of bodily activities, from growth to reproduction.
8. What three types of signals control hormone secretion?
Types of Anterior Pituitary Cells and Their

Hormones Five types of anterior pituitary cells—somatotrophs,
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thyrotrophs, gonadotrophs, lactotrophs, and corticotrophs—secrete
seven hormones (Table 18.3):
18.6 Hypothalamus and 1. Somatotrophs (sō-MAT-ō-trōfs) secrete growth hormone (GH),
Pituitary Gland
ile
also known as human growth hormone (hGH) or somatotropin (sō′-
-
ma-tō-TRO-pin; somato- = body; -tropin = change). Growth hor-
mone stimulates general body growth and regulates aspects of
OBJECTIVES metabolism.
-
2. Thyrotrophs (THI -rō-trōfs) secrete thyroid-stimulating hormone
• Describe the locations of and relationships between the -
(TSH), also known as thyrotropin (thī-rō-TRO-pin; thyro- = pertain-
hypothalamus and pituitary gland.
y,
ing to the thyroid gland). TSH controls the secretions and other
• Describe the location, histology, hormones, and functions of the activities of the thyroid gland.
anterior and posterior pituitary.
3. Gonadotrophs (gō-NAD-ō-trōfs; gonado- = seed) secrete two
gonadotropins: follicle-stimulating hormone (FSH) and lute-
inizing hormone (LH) (LOO-tē-in′-īz-ing). FSH and LH both act
For many years, the pituitary gland (pi-TOO-i-tār-ē) or hypophysis
on the gonads (testes and ovaries). In men, they stimulate the
20
(hī-POF-i-sis) was called the “master” endocrine gland because it
testes to produce sperm and to secrete testosterone. In women,
secretes several hormones that control other endocrine glands. We
they stimulate the ovaries to mature oocytes (eggs) and to
now know that the pituitary gland itself has a master—the hypothal-
secrete estrogens and progesterone.
amus. This small region of the brain below the thalamus is the major
link between the nervous and endocrine systems. Cells in the hypo- 4. Lactotrophs (LAK-tō-trōfs; lacto- = milk) secrete prolactin (PRL),
thalamus synthesize at least nine different hormones, and the pitu- which initiates milk production in the mammary glands.
20
itary gland secretes seven. Together, these hormones play important 5. Corticotrophs (KOR-ti-kō-trōfs) secrete adrenocorticotropic
-
roles in the regulation of virtually all aspects of growth, development, hormone (ACTH), also known as corticotropin (kor′-ti-kō-TRO-
metabolism, and homeostasis. pin; cortico- = rind or bark), which stimulates the adrenal cortex
The pituitary gland is a pea-shaped structure that measures to secrete glucocorticoids such as cortisol. Some corticotrophs,
1–1.5 cm (0.5 in.) in diameter and lies in the hypophyseal fossa of the remnants of the pars intermedia, also secrete melanocyte-
sella turcica of the sphenoid bone. It attaches to the hypothalamus stimulating hormone (MSH).
597
18.6 Hypothalamus and Pituitary Gland 631
FIGURE 18.5 Hypothalamus and pituitary gland.
Hypothalamic hormones are an important link between the nervous and endocrine systems.
C
Infundibulum
op
Posterior
pituitary
Anterior
pituitary
Sagittal section of pituitary gland

Dissection Shawn Miller, Photograph Mark Nielsen
yr
Hypothalamus
Pituitary gland
ig
Primary plexus of the

hypophyseal portal system
Hypothalamus
ht
Infundibulum Median eminence
Superior
hypophyseal
artery
Hypophyseal portal
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Hypophyseal veins
veins
Sphenoid bone
Posterior
pituitary Anterior pituitary
ile
Secondary plexus
Capillary plexus of the hypophyseal
of the infundibular portal system
process
Hypophyseal
Hypophyseal veins
fossa
y,
ANTERIOR
Inferior hypophyseal artery
(a) Relationship of the hypothalamus to the pituitary gland

20
Hypothalamic Control of the Anterior Pituitary 2. Thyrotropin-releasing hormone (TRH) stimulates secretion of
Release of anterior pituitary hormones is regulated in part by thyroid-stimulating hormone.
the hypothalamus. The hypothalamus secretes five releasing
20
3. Corticotropin-releasing hormone (CRH) stimulates secretion of
hormones, which stimulate secretion of anterior pituitary hormones adrenocorticotropic hormone.
(Table 18.3): 4. Prolactin-releasing hormone (PRH) stimulates secretion of
prolactin.
1. Growth hormone-releasing hormone (GHRH), also known as 5. Gonadotropin-releasing hormone (GnRH) stimulates secretion of
somatocrinin, stimulates secretion of growth hormone. FSH and LH.
598
Hypothalamus
C
Posterior pituitary Anterior pituitary

Somatotroph Hypothalamic neurosecretory cells
op
(secretes GH)
Corticotroph
(secretes ACTH) Thyrotroph
(secretes TSH)
1 Hypothalamus
Gonadotroph
Lactotroph (secretes FSH
(secretes PRL) and LH)
yr
Anterior pituitary cell types Releasing hormone
and their hormones Inhibiting hormone Optic chiasm
2
Primary plexus Superior hypophyseal
artery
Hypophyseal Hypophyseal
ig
portal system portal veins 3
Anterior pituitary cell
Secondary
plexus Anterior pituitary
hormone
ht
Hypophyseal vein
4
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GH TSH ACTH PRL FSH and LH
ile
Bone Skeletal muscle Thyroid gland Adrenal gland Mammary glands Ovaries Testes
(b) Hypothalamic control of anterior pituitary hormone secretion

y,
Q What is the functional importance of the hypophyseal portal veins?
The hypothalamus also produces two inhibiting hormones, portal system, blood flows from one capillary network into a portal
20
which suppress secretion of anterior pituitary hormones: vein and then into a second capillary network before returning to the
heart. The name of the portal system indicates the location of the
1. Growth hormone-inhibiting hormone (GHIH), also known as second capillary network. In the hypophyseal portal system (hī′-pō-
somatostatin, suppresses secretion of growth hormone. FIZ-ē-al), blood flows from capillaries in the hypothalamus into portal
2. Prolactin-inhibiting hormone (PIH), which is dopamine, sup- veins that carry blood to capillaries of the anterior pituitary. In other
presses secretion of prolactin. words, the hormones carried by the system allow communication
20
between the hypothalamus and anterior pituitary and establish
an important link between the nervous system and the endocrine
Hypophyseal Portal System Hypothalamic hormones system.
that release or inhibit anterior pituitary hormones reach the anterior The superior hypophyseal arteries, branches of the internal ca-
pituitary through a portal system. Usually, blood passes from the heart rotid arteries, bring blood into the hypothalamus (Figure 18.5a). At
through an artery to a capillary to a vein and back to the heart. In a the junction of the median eminence of the hypothalamus and the
599
TA B LE 1 8 . 3 Hormones and Cells of the Anterior Pituitary
HYPOTHALAMIC RELEASING HORMONE HYPOTHALAMIC INHIBITING HORMONE

C
HORMONE SECRETED BY (STIMULATES SECRETION) (SUPPRESSES SECRETION)
Growth hormone (GH), Somatotrophs Growth hormone-releasing hormone (GHRH), Growth hormone-inhibiting hormone (GHIH),
also known as somatotropin also known as somatocrinin. also known as somatostatin.
op
Thyroid-stimulating hormone (TSH), Thyrotrophs Thyrotropin-releasing hormone (TRH). Growth hormone-inhibiting hormone (GHIH).
also known as thyrotropin
Follicle-stimulating hormone (FSH) Gonadotrophs. Gonadotropin-releasing hormone (GnRH). —
Luteinizing hormone (LH) Gonadotrophs. Gonadotropin-releasing hormone (GnRH). —

yr
Prolactin (PRL) Lactotrophs Prolactin-releasing hormone (PRH).* Prolactin-inhibiting hormone (PIH), which is
dopamine.
Adrenocorticotropic hormone Corticotrophs. Corticotropin-releasing hormone (CRH). —

(ACTH), also known as
corticotropin
ig
Melanocyte-stimulating Corticotrophs. Corticotropin-releasing hormone (CRH). Dopamine.
hormone (MSH)
*Thought to exist, but exact nature is uncertain.

ht
Corticotroph
Thyrotroph
Lactotroph
Somatotroph
Gonadotroph
LM all about 65x Courtesy James Lowe, University of Nottingham, Nottingham, United Kingdom
W
Histology of anterior pituitary
infundibulum, these arteries divide into a capillary network called secondary plexus. This direct route permits hypothalamic
ile
the primary plexus of the hypophyseal portal system. From the hormones to act immediately on anterior pituitary cells, before
primary plexus, blood drains into the hypophyseal portal veins the hormones are diluted or destroyed in the general circulation.
that pass down the outside of the infundibulum. In the anterior Within the secondary plexus the hypothalamic hormones diffuse
pituitary, the hypophyseal portal veins divide again and form another out of the bloodstream and interact with anterior pituitary cells.
capillary network called the secondary plexus of the hypophyseal When stimulated by the appropriate hypothalamic-releasing
portal system. Hypophyseal veins drain blood from the anterior hormones, the anterior pituitary cells secrete hormones into the
y,
pituitary. secondary plexus capillaries.
4 From the secondary plexus capillaries, the anterior pituitary
Control of Anterior Pituitary Secretion Regulation hormones drain into the hypophyseal veins and out into the
of anterior pituitary secretion by the hypothalamus occurs as follows general circulation. Anterior pituitary hormones then travel to
(Figure 18.5b): target tissues throughout the body. Those anterior pituitary
20
hormones that act on other endocrine glands are called tropic
1 Above the optic chiasm are clusters of neurons called -
hormones (TRO-pik) or tropins.
neurosecretory cells. They synthesize the hypothalamic releasing
and inhibiting hormones in their cell bodies and package the Release of anterior pituitary hormones is regulated not only by
hormones inside vesicles, which reach the axon terminals by fast the hypothalamus (see Table 18.3) but also by negative feedback.
axonal transport (see Section 12.2), where they are stored. The secretory activity of three types of anterior pituitary cells (thyro-
20
2 When the neurosecretory cells of the hypothalamus are excited, trophs, corticotrophs, and gonadotrophs) decreases when blood
nerve impulses trigger exocytosis of the vesicles. The hypo- levels of their target gland hormones rise. For example, adrenocorti-
thalamic hormones then diffuse into the blood of the primary cotropic hormone (ACTH) stimulates the cortex of the adrenal gland
plexus of the hypophyseal portal system. to secrete glucocorticoids, mainly cortisol (Figure 18.6). In turn, an
3 Quickly, the hypothalamic hormones are transported by the elevated blood level of cortisol decreases secretion of both ACTH
blood through the hypophyseal portal veins and into the (corticotropin) and corticotropin-releasing hormone (CRH) by
600
FIGURE 18.6 Negative feedback regulation of hypothalamic act locally as autocrines or paracrines to cause growth of those
neurosecretory cells and anterior pituitary corticotrophs. Solid green tissues. Unlike the effects of GH on body growth, the effects of GH on
arrows indicate stimulation of secretions; dashed red arrows indicate metabolism are direct, meaning that GH interacts directly with target
C
inhibition of secretion via negative feedback. cells to cause specific metabolic reactions.
Using IGFs as mediators, GH causes growth of bones and other
Cortisol secreted by the adrenal cortex suppresses secretion of CRH and
tissues of the body. Through direct effects, GH helps regulate certain
ACTH.
op
metabolic reactions in body cells. The specific functions of IGFs and
GH include the following:
Corticotropin-releasing
1. Increase growth of bones and soft tissues. In bones, IGFs stimulate
hormone (CRH) osteoblasts, promote cell division at the epiphyseal plate, and en-
hance synthesis of the proteins needed to build more bone matrix.
In soft tissues such as skeletal muscle, the kidneys, and intestines,
yr
Hypothalamus
IGFs cause cells to grow by increasing uptake of amino acids into
Elevated cortisol cells and accelerating protein synthesis. IGFs also decrease the
CRH stimulates inhibits release
of CRH by breakdown of proteins and the use of amino acids for ATP pro-
release of ACTH
corticotropin hypothalamic duction. Due to the effects of IGFs, GH increases growth of the
neurosecretory
ig
cells
skeleton and soft tissues during childhood and the teenage
years. In adults, GH (acting via IGFs) helps maintain the mass of
Anterior bones and soft tissues and promotes healing of injuries and
pituitary Corticotropin
(ACTH) tissue repair.
2. Enhance lipolysis. GH enhances lipolysis in adipose tissue, which
ht
Elevated cortisol
results in increased use of the released fatty acids for ATP
inhibits release production by body cells.
of ACTH
ACTH stimulates by anterior 3. Decrease glucose uptake. GH influences carbohydrate metabolism
secretion of cortisol by pituitary by decreasing glucose uptake, which decreases the use of glucose
adrenal cortex corticotrophs for ATP production by most body cells. This action spares glucose
so that it is available to neurons for ATP production in times of
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glucose scarcity. GH also stimulates liver cells to release glucose
Adrenal
cortex into the blood.
Somatotrophs in the anterior pituitary release bursts of growth

hormone every few hours, especially during sleep. Their secretory
ile
activity is controlled mainly by two hypothalamic hormones:
(1) growth hormone-releasing hormone (GHRH) promotes secretion
Cortisol of growth hormone and (2) growth hormone-inhibiting hormone
(GHIH) suppresses it. Regulation of growth hormone secretion by
Q Which other target gland hormones suppress secretion of GHRH and GHIH occurs as follows (Figure 18.7).
hypothalamic and anterior pituitary hormones by negative
y,
feedback? 1 GHRH is secreted from the hypothalamus. Factors that promote
GHRH secretion include hypoglycemia (low blood glucose
concentration); decreased blood levels of fatty acids; increased
suppressing the activity of the anterior pituitary corticotrophs and blood levels of amino acids; deep sleep (stages 3 and 4 of non-
hypothalamic neurosecretory cells. rapid eye movement sleep); increased activity of the sympathetic
nervous system, such as might occur with stress or vigorous
20
physical exercise; and other hormones, including testosterone,
Growth Hormone Somatotrophs are the most numerous
estrogens, thyroid hormones, and ghrelin.
cells in the anterior pituitary, and growth hormone (GH) is the most
2 Once secreted, GHRH enters the hypophyseal portal system and
plentiful anterior pituitary hormone. GH promotes growth of body
flows to the anterior pituitary, where it stimulates somatotrophs
tissues, including bones and skeletal muscles, and it regulates certain
to secrete GH.
aspects of metabolism. GH exerts its growth-promoting effects
20
indirectly through small protein hormones called insulin-like growth 3 GH acts directly on various cells to promote certain metabolic
- reactions. In liver, bone, skeletal muscle, and cartilage, GH is con-
factors (IGFs) or somatomedins (sō′-ma-tō-ME -dins). In response
to growth hormone, cells in the liver, skeletal muscle, cartilage, and verted to IGFs, which in turn promote growth of bones, skeletal
bone secrete IGFs. IGFs synthesized in the liver enter the bloodstream muscle, and other tissues.
as hormones that circulate to target cells throughout the body to 4 Elevated levels of GH and IGFs inhibit release of GHRH and GH
cause growth. IGFs produced in skeletal muscle, cartilage, and bone (negative feedback inhibition).
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FIGURE 18.7 Regulation of growth hormone (GH) secretion. Each somatotrophs from secreting GH by interfering with the signaling
dashed arrow and negative sign indicates negative feedback. pathway used by GHRH.
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Secretion of GH is stimulated by growth hormone–releasing hormone Clinical Connection
(GHRH) and inhibited by growth hormone–inhibiting hormone (GHIH).
Diabetogenic Effect of GH
op
One symptom of excess growth hormone (GH) is hyperglycemia. Persistent
• Hypoglycemia • Hyperglycemia hyperglycemia in turn stimulates the pancreas to secrete insulin continu-
• Decreased blood levels of fatty • Increased blood levels of fatty ally. Such excessive stimulation, if it lasts for weeks or months, may cause
acids acids
• Increased blood levels of amino • Decreased blood levels of “beta-cell burnout,” a greatly decreased capacity of pancreatic beta cells to
acids amino acids synthesize and secrete insulin. Thus, excess secretion of growth hormone
• Sympathetic activity • Obesity may have a diabetogenic effect (dī′-a-bet′-o-JEN-ik); that is, it causes dia-
• Deep sleep • Aging
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betes mellitus (lack of insulin activity).
• Testosterone, estrogens, thyroid • High blood levels of GH and
hormones, and ghrelin IGFs
Hypothalamus
1 5
Thyroid-Stimulating Hormone Thyroid-stimulating hor-
mone (TSH) stimulates the synthesis and secretion of the two thyroid
ig
GHRH GHIH
hormones, triiodothyronine (T3) and thyroxine (T4), both produced
by the thyroid gland. Thyrotropin-releasing hormone (TRH) from the
hypothalamus controls TSH secretion. Release of TRH in turn depends
on blood levels of T3 and T4; high levels of T3 and T4 inhibit secretion
ht
– 2 6 of TRH via negative feedback. There is no thyrotropin-inhibiting
hormone. The release of TRH is explained later in the chapter (see
4
Figure 18.12).
Anterior
GH No GH pituitary
secretion Follicle-Stimulating Hormone In females, the ovaries
are the targets for follicle-stimulating hormone (FSH). Each month
W
– 3
FSH initiates the development of several ovarian follicles, saclike
arrangements of secretory cells that surround a developing egg
4 (oocyte). FSH also stimulates follicular cells to secrete estrogens
Metabolic effects
on cells (female sex hormones). In males, FSH stimulates sperm production
in the testes. Gonadotropin-releasing hormone (GnRH) from the
ile
hypothalamus stimulates FSH release. Release of GnRH and FSH is
Liver, bone, skeletal suppressed by estrogens in females and by testosterone (the principal
muscle, and cartilage
male sex hormone) in males through negative feedback systems.
There is no gonadotropin-inhibiting hormone.
Luteinizing Hormone In females, luteinizing hormone

y,
IGFs
(LH) triggers ovulation, the release of a secondary oocyte (future
ovum) by an ovary. LH stimulates formation of the corpus luteum
Growth of bone, muscle, (structure formed after ovulation) in the ovary and the secretion of
and other tissues progesterone (another female sex hormone) by the corpus luteum.
Q If a person has a pituitary tumor that secretes a large Together, FSH and LH also stimulate secretion of estrogens by
20
amount of GH and the tumor cells are not responsive ovarian cells. Estrogens and progesterone prepare the uterus for
to regulation by GHRH and GHIH, will hyperglycemia or implantation of a fertilized ovum and help prepare the mammary
hypoglycemia be more likely? glands for milk secretion. In males, LH stimulates cells in the testes to
secrete testosterone. Secretion of LH, like that of FSH, is controlled by
gonadotropin-releasing hormone (GnRH).
20
5 GHIH is secreted from the hypothalamus. Factors that promote Prolactin Prolactin (PRL), together with other hormones, initiates
GHIH secretion include hyperglycemia (high blood glucose); and maintains milk production by the mammary glands. By itself,
increased blood levels of fatty acids; decreased blood levels of prolactin has only a weak effect. Only after the mammary glands have
amino acids; obesity; aging; and high blood levels of GH and IGFs. been primed by estrogens, progesterone, glucocorticoids, growth
6 After being secreted, GHIH enters the hypophyseal portal hormone, thyroxine, and insulin, which exert permissive effects, does
system and flows to the anterior pituitary, where it prevents the PRL bring about milk production. Ejection of milk from the mammary
602
glands depends on the hormone oxytocin, which is released from the Adrenocorticotropic Hormone Corticotrophs secrete
posterior pituitary. Together, milk production and ejection constitute mainly adrenocorticotropic hormone (ACTH). ACTH controls the
lactation. production and secretion of cortisol and other glucocorticoids by the
C
The hypothalamus secretes both inhibitory and excitatory cortex (outer portion) of the adrenal glands. Corticotropin-releasing
hormones that regulate prolactin secretion. In females, prolactin- hormone (CRH) from the hypothalamus stimulates secretion of ACTH
inhibiting hormone (PIH), which is dopamine, inhibits the release by corticotrophs. Stress-related stimuli, such as low blood glucose
op
of prolactin from the anterior pituitary most of the time. Each or physical trauma, and interleukin-1, a substance produced by
month, just before menstruation begins, the secretion of PIH macrophages, also stimulate release of ACTH. Glucocorticoids inhibit
diminishes and the blood level of prolactin rises, but not enough CRH and ACTH release via negative feedback.
to stimulate milk production. Breast tenderness just before men-
struation may be caused by elevated prolactin. As the menstrual Melanocyte-Stimulating Hormone Melanocyte-stimulating
cycle begins anew, PIH is again secreted and the prolactin level hormone (MSH) increases skin pigmentation in amphibians by stimulating
yr
drops. During pregnancy, the prolactin level rises, stimulated by the dispersion of melanin granules in melanocytes. Its exact role in
prolactin-releasing hormone (PRH) from the hypothalamus. The humans is unknown, but the presence of MSH receptors in the brain
sucking action of a nursing infant causes a reduction in hypotha- suggests it may influence brain activity. There is little circulating
lamic secretion of PIH. MSH in humans. However, continued administration of MSH for
The function of prolactin is not known in males, but its hyperse- several days does produce a darkening of the skin. Excessive levels
ig
cretion causes erectile dysfunction (impotence, the inability to have of corticotropin-releasing hormone (CRH) can stimulate MSH release;
an erection of the penis). In females, hypersecretion of prolactin causes dopamine inhibits MSH release.
galactorrhea (inappropriate lactation) and amenorrhea (absence of Table 18.4 summarizes the principal actions of the anterior
menstrual cycles). pituitary hormones.
ht
TA B L E 1 8 . 4 Summary of the Principal Actions of Anterior Pituitary Hormones
HORMONE TARGET TISSUES PRINCIPAL ACTIONS

Growth hormone (GH), also Stimulates liver, muscle, cartilage, bone, and other tissues to synthesize and secrete
known as somatotropin insulin-like growth factors (IGFs), which in turn promote growth of body tissues. GH
W
acts directly on target cells to enhance lipolysis and decrease glucose uptake.
Liver (and other tissues)
Thyroid-stimulating Stimulates synthesis and secretion of thyroid hormones by thyroid gland.

hormone (TSH), also
ile
known as thyrotropin
Thyroid gland
Follicle-stimulating In females, initiates development of oocytes and induces ovarian secretion of estrogens.
hormone (FSH) In males, stimulates testes to produce sperm.
y,
Ovary Testis
Luteinizing In females, stimulates secretion of estrogens and progesterone, ovulation, and formation
hormone (LH) of corpus luteum. In males, stimulates testes to produce testosterone.
Ovary Testis
20
Prolactin (PRL) Together with other hormones, promotes milk production by mammary glands.
Mammary glands
Adrenocorticotropic Stimulates secretion of glucocorticoids (mainly cortisol) by adrenal cortex.

20
hormone (ACTH), Adrenal
also known as cortex
corticotropin
Melanocyte-stimulating Exact role in humans is unknown but may influence brain activity; when present in
hormone (MSH) excess, can cause darkening of skin.
Brain
603
Posterior Pituitary Control of Posterior Pituitary Secretion Release of

hormones from the posterior pituitary occurs as follows (Figure 18.8b):
Although the posterior pituitary does not synthesize hormones, it does
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1 Neurosecretory cells in the paraventricular and supraoptic
store and release two hormones. It consists of axons and axon terminals
of more than 10,000 hypothalamic neurosecretory cells. The cell bodies nuclei of the hypothalamus synthesize oxytocin and antidiuretic
of the neurosecretory cells are in the paraventricular and supraoptic hormone (ADH). The hormones are then packaged into vesicles.
op
nuclei of the hypothalamus; their axons form the hypothalamic– 2 The vesicles move by fast axonal transport along the
hypophyseal tract (hī′-pō-THAL-a-mik hī-pō-FIZ-ē-al). This tract begins hypothalamic–hypophyseal tract to the axon terminals in the
in the hypothalamus and ends near blood capillaries in the posterior posterior pituitary, where they are stored.
pituitary (Figure 18.8a). The neuronal cell bodies of both the paraven- 3 When the appropriate stimulus excites the hypothalamus, nerve
tricular and the supraoptic nuclei synthesize the hormones oxytocin impulses trigger exocytosis and release of oxytocin or ADH into
-
(OT) (ok′-sē-TO-sin; okytoc = quick birth) and antidiuretic hormone the bloodstream (inferior hypophyseal artery, capillary plexus of
yr
(ADH), also called vasopressin (vā-sō-PRES-in; vaso- = blood; -pressus = the infundibular process, and hypophyseal vein).
to press). The axon terminals in the posterior pituitary are associated
4 The released oxytocin or ADH then travels to its target tissues in
with specialized neuroglia called pituicytes (pi-TOO-i-sītz). These cells
the body.
have a supporting role similar to that of astrocytes (see Chapter 12).
Blood is supplied to the posterior pituitary by the inferior hypo-
ig
physeal arteries, which branch from the internal carotid arteries. In Oxytocin During and after delivery of a baby, oxytocin affects
the posterior pituitary, the inferior hypophyseal arteries drain into the two target tissues: the mother’s uterus and breasts. During delivery,
capillary plexus of the infundibular process, a capillary network stretching of the cervix of the uterus stimulates the release of oxytocin
that receives secreted oxytocin and antidiuretic hormone (see which, in turn, enhances contraction of smooth muscle cells in the wall
ht
Figure 18.5). From this plexus, hormones pass into the hypophyseal of the uterus (see Figure 1.5); after delivery, it stimulates milk ejection
veins for distribution to target cells in other tissues. (“letdown”) from the mammary glands in response to the mechanical
FIGURE 18.8 The hypothalamic–hypophyseal tract and regulation of hormone release by the
posterior pituitary.
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Oxytocin and antidiuretic hormone are synthesized in the hypothalamus and released into the
capillary plexus of the infundibular process in the posterior pituitary.
ile
Hypothalamus Cell bodies of

neurosecretory
cells
Pituitary gland
Hypothalamus
Optic
y,
chiasm
Infundibulum
Hypothalamic–hypophyseal
(axons of neurosecretory cells)
20
tract
Axon terminal
Posterior Anterior
20
pituitary pituitary
(a) Hypothalamic–hypophyseal tract Figure 18.8 Continues
604
FIGURE 18.8 Continued

Paraventricular Neurosecretory cells Supraoptic
nucleus nucleus
C
1
op
Hypothalamus
Oxytocin
ADH
yr
2
Hypothalamic–hypophyseal
tract
3
Inferior hypophyseal artery
ig
Capillary plexus of infundibular
process
Hypophyseal vein
ht
4
Oxytocin ADH
W
ile
Uterus Mammary glands Kidneys Arterioles
(b) Release of hormones from posterior pituitary
Q Functionally, how are the hypothalamic–hypophyseal tract and the hypophyseal
portal veins similar? Structurally, how are they different?
y,
stimulus provided by a suckling infant. The function of oxytocin in males Antidiuretic Hormone As its name implies, an antidiu-
and in nonpregnant females is not clear. Experiments with animals retic (an-ti-dī-ū-RET-ik; anti- = against; -dia- = throughout; -ouresis
have suggested that it has actions within the brain that foster parental = urination) is a substance that decreases urine production. ADH
caretaking behavior toward young offspring. It may also be responsible, causes the kidneys to return more water to the blood, thus decreas-
in part, for the feelings of sexual pleasure during and after intercourse. ing urine volume. In the absence of ADH, urine output increases
20
more than tenfold, from the normal 1 to 2 liters to about 20 liters a
Clinical Connection day. Drinking alcohol often causes frequent and copious urination
because alcohol inhibits secretion of ADH. (This dehydrating effect
of alcohol may cause both the thirst and the headache typical of
Oxytocin and Childbirth
a hangover.) ADH also decreases the water lost through sweating
Years before oxytocin was discovered, it was common practice in midwifery and causes constriction of arterioles, which increases blood pres-
20
to let a first-born twin nurse at the mother’s breast to speed the birth of the sure. This hormone’s other name, vasopressin, reflects this effect on
second child. Now we know why this practice is helpful—it stimulates the
blood pressure.
release of oxytocin. Even after a single birth, nursing promotes expulsion of
Two major stimuli promote ADH secretion: a rise in blood os-
the placenta (afterbirth) and helps the uterus regain its smaller size. Syn-
molarity and a decrease in blood volume. High blood osmolarity is
thetic oxytocin (Pitocin) often is given to induce labor or to increase uterine
tone and control hemorrhage just after giving birth. detected by osmoreceptors, neurons in the hypothalamus that
monitor changes in blood osmolarity. Decreased blood volume is
605
18.7 Thyroid Gland 639
TA B LE 1 8 . 5 Summary of Posterior Pituitary Hormones
HORMONE AND
C
TARGET TISSUES CONTROL OF SECRETION PRINCIPAL ACTIONS
Oxytocin (OT) Neurosecretory cells of hypothalamus secrete OT in Stimulates contraction of smooth muscle cells of
response to uterine distension and stimulation of uterus during childbirth; stimulates contraction of
op
nipples. myoepithelial cells in mammary glands to cause
milk ejection.
Uterus Mammary glands
Antidiuretic hormone Neurosecretory cells of hypothalamus secrete ADH Conserves body water by decreasing urine volume;
yr
(ADH) or vasopressin in response to elevated blood osmotic pressure, decreases water loss through perspiration; raises
dehydration, loss of blood volume, pain, or stress; blood pressure by constricting arterioles.
inhibitors of ADH secretion include low blood
osmotic pressure, high blood volume, and alcohol.
ig
Kidneys Sudoriferous
(sweat) glands
ht
Arterioles
W
detected by volume receptors in the atria of the heart and by

baroreceptors in the walls of certain blood vessels. Once stimu- 18.7 Thyroid Gland
lated, osmoreceptors, atrial volume receptors, and baroreceptors
ile
activate the hypothalamic neurosecretory cells that synthesize
and release ADH into the bloodstream. Blood carries ADH to two OBJECTIVE
target tissues: the kidneys and smooth muscle in blood vessel
walls. The kidneys respond by retaining more water, which de- • Describe the location, histology, hormones, and functions of the
creases urine output. Smooth muscle in the walls of arterioles thyroid gland.
(small arteries) contracts in response to high levels of ADH, which
y,
constricts (narrows) the lumen of these blood vessels and in-
creases blood pressure. The butterfly-shaped thyroid gland is located just inferior to the
Secretion of ADH can be altered in other ways as well. Pain, stress, larynx (voice box). It is composed of right and left lateral lobes, one
trauma, anxiety, acetylcholine, nicotine, and drugs such as morphine, on either side of the trachea, that are connected by an isthmus
tranquilizers, and some anesthetics stimulate ADH secretion. (IS-mus = a narrow passage) anterior to the trachea (Figure 18.9a).
Table 18.5 lists the posterior pituitary hormones, control of their About 50% of thyroid glands have a small third lobe, called the pyra-
20
secretion, and their principal actions. midal lobe. It extends superiorly from the isthmus. The normal mass
of the thyroid is about 30 g (1 oz).
Microscopic spherical sacs called thyroid follicles (Figure 18.9b)
make up most of the thyroid gland. The wall of each follicle consists
Checkpoint primarily of cells called follicular cells (fo-LIK-ū-lar), most of which
extend to the lumen (internal space) of the follicle. A basement mem-
20
9. In what respect is the pituitary gland actually two glands? brane surrounds each follicle. When the follicular cells are inactive,
10. How do hypothalamic releasing and inhibiting hormones their shape is low cuboidal to squamous, but under the influence of
influence secretions of the anterior pituitary? TSH they become active in secretion and range from cuboidal to low
columnar in shape. The follicular cells produce two hormones: thy-
11. Describe the structure and importance of the hypothalamic–
hypophyseal tract. roxine (thī-ROK-sēn), which is also called tetraiodothyronine (T4) (tet-
-
ra-ī-ō-dō-THI -rō-nēn) because it contains four atoms of iodine, and
606
FIGURE 18.9 Location, blood supply, and histology of the thyroid gland.
Thyroid hormones regulate (1) oxygen use and basal metabolic rate, (2) cellular metabolism, and
(3) growth and development.
C
Hyoid bone
Superior thyroid artery
Superior thyroid vein

op
Thyroid
gland Thyroid cartilage of larynx
Trachea Pyramidal lobe of
thyroid gland Internal jugular vein
Right lateral lobe Left lateral lobe
of thyroid gland of thyroid gland
Common carotid artery
Middle thyroid vein
yr
Isthmus of thyroid
Inferior thyroid artery gland
Vagus (X) nerve
Subclavian artery
Trachea
ig
Inferior thyroid veins
Sternum
ht
(a) Anterior view of thyroid gland

Parafollicular (C)
cell
Follicular cell
W
Thyroid follicle Right lateral Left lateral
lobe lobe
Thyroglobulin Isthmus Left lateral

Right lateral
(TGB) (colloid) lobe lobe
ile
Basement membrane Isthmus

(c) Anterior view of thyroid gland
Mark Nielsen LM 500x
Thyroid cartilage of larynx
(b) Thyroid follicles (c) Anterior view of thyroid gland
y,
Cricoid cartilage of larynx

Right lateral lobe of thyroid gland
Left lateral lobe of thyroid gland
20
Isthmus of thyroid gland
Trachea
20
Right lung
Arch of aorta
Q Which cells secrete T3 and T4?
Which secrete calcitonin? Which
640 Dissection Shawn Miller, Photograph Mark Nielsen of these hormones are also called
(d) Anterior view thyroid hormones?
607
18.7 Thyroid Gland 641
-
triiodothyronine (T3) (trī-ī′-ō-dō-THI -rō-nēn), which contains three FIGURE 18.10 Steps in the synthesis and secretion of thyroid
atoms of iodine. T3 and T4 together are also known as thyroid hor-
hormones.
mones. A few cells called parafollicular cells (par′-a-fo-LIK-ū-lar) or
C
C cells lie between follicles. They produce the hormone calcitonin
Thyroid hormones are synthesized by attaching iodine atoms to the
- amino acid tyrosine.
(CT) (kal-si-TO -nin), which helps regulate calcium homeostasis.
Formation, Storage, and Release

op
Portion of thyroid follicle
of Thyroid Hormones Follicular
4 Iodination Colloid cell
The thyroid gland is the only endocrine gland that stores its secretory of tyrosine Blood
product in large quantities—normally about a 100-day supply. Syn- capillary
thesis and secretion of T3 and T4 occurs as follows (Figure 18.10): I
yr
− 5 Coupling
1 Iodide trapping. Thyroid follicular cells trap iodide ions (I ) by actively
I
I
I
I I
I of T1 and T2
transporting them from the blood into the cytosol. As a result, the
I
I
Tyrosine
I
I
I
thyroid gland normally contains most of the iodide in the body. I T1
I I
I
I
I
I
T2
2 Synthesis of thyroglobulin. While the follicular cells are trapping I I
ig
I
I
I
I
I−, they are also synthesizing thyroglobulin (TGB) (thī′-rō-
I
I
I
I
I
I
I
GLOB-u-lin), a large glycoprotein that is produced in the rough I
I
T4
I
I
endoplasmic reticulum, modified in the Golgi complex, and I
I
I
I
I
3 Oxidation
I
packaged into secretory vesicles. The vesicles then undergo
I
Colloid T3
I
ht
of iodide
exocytosis, which releases TGB into the lumen of the follicle. 0
I I
I
3 Oxidation of iodide. Some of the amino acids in TGB are tyrosines TGB
that will become iodinated. However, negatively charged iodide

ions cannot bind to tyrosine until they undergo oxidation (removal
of electrons) to iodine: I−→ I0. As the iodide ions are being oxidized, 6 Pinocytosis
they pass through the membrane into the lumen of the follicle. and digestion
of colloid
W
4 Iodination of tyrosine. As iodine atoms (I0) form, they react
with tyrosines that are part of thyroglobulin molecules. Binding
of one iodine atom yields monoiodotyrosine (T1), and a second
Secretory
iodination produces diiodotyrosine (T2). The TGB with attached vesicles
Lysosome
ile
iodine atoms, a sticky material that accumulates and is stored in
the lumen of the thyroid follicle, is termed colloid.
Golgi complex
5 Coupling of T1 and T2. During the last step in the synthesis of T3
– – T4
thyroid hormone, two T2 molecules join to form T4, or one T1 and – I I
I 2 Synthesis
one T2 join to form T3. I– I
– of TGB
–
I T3
6 Pinocytosis and digestion of colloid. Droplets of colloid reenter T4
y,
I– I– Rough ER
follicular cells by pinocytosis and merge with lysosomes.
7 Secretion
Digestive enzymes in the lysosomes break down TGB, cleaving off 1 Iodide of thyroid
molecules of T3 and T4. trapping hormones
I–
7 Secretion of thyroid hormones. Because T3 and T4 are lipid- –
I T3 TBG
soluble, they diffuse through the plasma membrane into
I– Blood T4 TBG
20
interstitial fluid and then into the blood. T4 normally is secreted plasma 8 Transport
in greater quantity than T3, but T3 is several times more potent. Key: in blood
Moreover, after T4 enters a body cell, most of it is converted to T3 I – = Iodide; I0 = iodine
TGB = thyroglobulin Blood capillary
by removal of one iodine. TBG = thyroxine-binding globulin
8 Transport in the blood. More than 99% of both the T3 and the T4
Q What is the storage form of thyroid hormones?
combine with transport proteins in the blood, mainly thyroxine-
20
binding globulin (TBG). target cells mainly by inducing gene transcription and protein synthe-
sis. The newly formed proteins in turn carry out the cellular response.
Actions of Thyroid Hormones Functions of thyroid hormones include the following:
Because most body cells have receptors for thyroid hormones, T3 and 1. Increase basal metabolic rate. Thyroid hormones raise the basal
T4 affect tissues throughout the body. Thyroid hormones act on their metabolic rate (BMR), the rate of energy expenditure under
608
standard or basal conditions (awake, at rest, and fasting). When FIGURE 18.11 Regulation of secretion and actions of thyroid
BMR increases, cellular metabolism of carbohydrates, lipids, and hormones. TRH = thyrotropin-releasing hormone, TSH = thyroid-
proteins increases. Thyroid hormones increase BMR in several stimulating hormone, T3 = triiodothyronine, and T4 = thyroxine
C
ways: (1) They stimulate synthesis of additional Na+/K+ ATPases, (tetraiodothyronine).
which use large amounts of ATP to continually eject sodium ions
TSH promotes release of thyroid hormones (T3 and T4) by the thyroid
(Na+) from cytosol into extracellular fluid and potassium ions (K+)
gland.
op
from extracellular fluid into cytosol; (2) they increase the concen-
trations of enzymes involved in cellular respiration, which increas-
es the breakdown of organic fuels and ATP production; and (3) they 1 Low blood levels of T3
and T4 or low metabolic
increase the number and activity of mitochondria in cells, which rate stimulates release of
also increases ATP production. As cells produce and use more ATP,
BMR increases, more heat is given off, and body temperature rises,
yr
a phenomenon called the calorigenic effect. In this way, thyroid TRH Hypothalamus
hormones play an important role in the maintenance of normal
body temperature. Normal mammals can survive in freezing tem- 2 TRH, carried by
portal veins to
peratures, but those whose thyroid glands have been removed anterior pituitary,
cannot. stimulates release 5 Elevated
ig
of TSH by T3 inhibits
2. Enhance actions of catechlolamines. Thyroid hormones have per- thyrotrophs release of
missive effects on the catecholamines (epinephrine and norepi- – TRH and
TSH
nephrine) because they up-regulate β-adrenergic receptors. Recall TSH (negative
that catecholamines bind to β-adrenergic receptors, promoting feedback)
ht
sympathetic responses. Therefore, symptoms of excess levels of
thyroid hormone include increased heart rate, more forceful heart- 3 TSH released into Anterior
blood stimulates pituitary
beats, and increased blood pressure. thyroid follicular cells
3. Regulate development and growth of nervous tissue and bones. 4 T3 and T4
Thyroid hormones are necessary for the development of the ner- released into
blood by
vous system: They promote synapse formation, myelin production, follicular cells
W
and growth of dendrites. Thyroid hormones are also required for
growth of the skeletal system: They promote formation of ossifica-
tion centers in developing bones, synthesis of many bone proteins,
and secretion of growth hormone (GH) and insulin-like growth
factors (IGFs). Deficiency of thyroid hormones during fetal devel- Q How could an iodine-deficient diet lead to goiter, which is
ile
opment, infancy, or childhood causes severe mental retardation an enlargement of the thyroid gland?
and stunted bone growth.
Conditions that increase ATP demand—a cold environment, hypogly-

Control of Thyroid Hormone Secretion cemia, high altitude, and pregnancy—increase the secretion of the
y,
thyroid hormones.
Thyrotropin-releasing hormone (TRH) from the hypothalamus and
thyroid-stimulating hormone (TSH) from the anterior pituitary stimu-
late secretion of thyroid hormones, as shown in Figure 18.11: Calcitonin
1 Low blood levels of T3 and T4 or low metabolic rate stimulate the The hormone produced by the parafollicular cells of the thyroid
20
hypothalamus to secrete TRH. gland (see Figure 18.9b) is calcitonin (CT). CT can decrease the
2 TRH enters the hypothalamic–hypophyseal portal system and level of calcium in the blood by inhibiting the action of osteoclasts,
flows to the anterior pituitary, where it stimulates thyrotrophs to the cells that break down bone extracellular matrix. The secretion
secrete TSH. of CT is controlled by a negative feedback system (see Fig-
ure 18.13).
3 TSH stimulates virtually all aspects of thyroid follicular cell
When its blood level is high, calcitonin lowers the amount of
activity, including iodide trapping, hormone synthesis and
20
blood calcium and phosphates by inhibiting bone resorption
secretion, and growth of the follicular cells (see Figure 18.10).
(breakdown of bone extracellular matrix) by osteoclasts and by ac-
4 The thyroid follicular cells release T3 and T4 into the blood until celerating uptake of calcium and phosphates into bone extracellu-
the metabolic rate returns to normal. lar matrix. Miacalcin, a calcitonin extract derived from salmon that
5 An elevated level of T3 inhibits release of TRH and TSH (negative is 10 times more potent than human calcitonin, is prescribed to
feedback inhibition). treat osteoporosis.
609
18.8 Parathyroid Glands 643
TA B LE 1 8 . 6 Summary of Thyroid Gland Hormones
HORMONE AND SOURCE CONTROL OF SECRETION PRINCIPAL ACTIONS

C
T3 (triiodothyronine) Secretion is increased by thyrotropin-releasing Increase basal metabolic rate; stimulate synthesis
and T4 (thyroxine) or hormone (TRH), which stimulates release of of proteins; increase use of glucose and fatty acids
thyroid hormones thyroid-stimulating hormone (TSH) in response for ATP production; increase lipolysis; enhance
op
from follicular cells to low thyroid hormone levels, low metabolic cholesterol excretion; accelerate body growth;
rate, cold, pregnancy, and high altitudes; TRH contribute to development of nervous system.
Follicular and TSH secretions are inhibited in response to
Thyroid cells high thyroid hormone levels; high iodine level
follicle suppresses T3/T4 secretion.
Blood
vessel
yr
Calcitonin (CT) High blood Ca2+ levels stimulate secretion; low Lowers blood levels of Ca2+ and HPO42− by
from parafollicular cells blood Ca2+ levels inhibit secretion. inhibiting bone resorption by osteoclasts and by
accelerating uptake of calcium and phosphates
into bone extracellular matrix.
Thyroid
ig
follicle
Parafollicular
cells
ht
Table 18.6 summarizes the hormones produced by the thyroid gland are attached to each lateral thyroid lobe (Figure 18.12a), for a
gland, control of their secretion, and their principal actions. total of four.
W
Microscopically, the parathyroid glands contain two kinds of
Checkpoint epithelial cells (Figure 18.12b, c). The more numerous cells, called
chief cells or principal cells, produce parathyroid hormone (PTH),
12. Explain how blood levels of T3/T4, TSH, and TRH would change also called parathormone. The function of the other kind of cell,
ile
in a laboratory animal that has undergone a thyroidectomy called an oxyphil cell, is not known in a normal parathyroid gland.
(complete removal of its thyroid gland). However, its presence clearly helps to identify the parathyroid gland
13. How are the thyroid hormones synthesized, stored, and histologically due to its unique staining characteristics. Further-
secreted? more, in a cancer of the parathyroid glands, oxyphil cells secrete
14. How is the secretion of T3 and T4 regulated? excess PTH.
15. What are the physiological effects of the thyroid hormones?
y,
Parathyroid Hormone
Parathyroid hormone is the major regulator of the levels of calcium
(Ca2+), magnesium (Mg2+), and phosphate (HPO42−) ions in the
18.8 Parathyroid Glands blood. The specific action of PTH is to increase the number and
20
activity of osteoclasts. The result is elevated bone resorption, which
releases ionic calcium (Ca2+) and phosphates (HPO42−) into the
OBJECTIVE blood. PTH also acts on the kidneys. First, it slows the rate at which
Ca2+ and Mg2+ are lost from blood into the urine. Second, it
• Describe the location, histology, hormone, and functions of the increases loss of HPO42− from blood into the urine. Because more
parathyroid glands. HPO42− is lost in the urine than is gained from the bones, PTH
20
decreases blood HPO42− level and increases blood Ca2+ and Mg2+
levels. A third effect of PTH on the kidneys is to promote formation of
-
Partially embedded in the posterior surface of the lateral lobes of the the hormone calcitriol (kal′-si-TRI -ol), the active form of vitamin D.
thyroid gland are several small, round masses of tissue called the Calcitriol, also known as 1,25-dihydroxyvitamin D3, increases the
parathyroid glands (para- = beside). Each has a mass of about rate of Ca2+, HPO42−, and Mg2+ absorption from the gastrointestinal
40 mg (0.04 g). Usually, one superior and one inferior parathyroid tract into the blood.
610
FIGURE 18.12 Location, blood supply, and histology of the parathyroid glands.
Right internal
jugular vein
The parathyroid glands, normally four in number, are embedded in the
C
posterior surface of the thyroid gland. Right common
carotid artery
Middle cervical
op
sympathetic ganglion
Thyroid gland
Left superior
parathyroid gland Right superior
parathyroid gland
Esophagus Inferior cervical
yr
sympathetic ganglion
Left inferior
parathyroid gland Right inferior
parathyroid gland
Left inferior thyroid artery
Parathyroid
glands (behind Vagus (X) nerve
ig
thyroid gland) Left subclavian artery
Right brachiocephalic vein
Left subclavian vein Brachiocephalic trunk
Trachea
Left common carotid artery Trachea
ht
(a) Posterior view
Parathyroid
Capsule Chief cell Parathyroid
Venule Thyroid Oxyphil cell gland
W
Blood
capillary
Arteriole
ile
Chief cell
y,
Oxyphil cell
Follicular cell
Thyroid gland Blood vessel
Parafollicular cell
Mark Nielsen LM 240x
20
(b) Parathyroid gland (c) Portion of the thyroid gland (left) and parathyroid gland (right)
Left superior
parathyroid Pyramidal lobe
20
gland of thyroid gland
Thyroid gland
Left inferior
parathyroid Q What are the secretory products of (1) parafollicular cells of the
gland Dissection Shawn Miller, Photograph Mark Nielsen thyroid gland and (2) chief (principal) cells of the parathyroid
(d) Posterior view of parathyroid glands glands?
611
18.8 Parathyroid Glands 645
FIGURE 18.13 The roles of calcitonin (green arrows), parathyroid hormone (blue arrows),
and calcitriol (orange arrows) in calcium homeostasis.
1 High level of Ca2+ in blood 3 Low level of Ca2+ in blood
C
With respect to regulation of blood stimulates thyroid gland stimulates parathyroid gland
Ca2+ level, calcitonin and PTH have parafollicular cells to release chief cells to release more
antagonistic effects. more calcitonin (CT). parathyroid hormone (PTH).
op
6 Calcitriol stimulates
yr
increased absorption of
2+
Ca from foods, which
2+
increases blood Ca level.
ig
5 PTH also stimulates

the kidneys to release 4 Parathyroid hormone (PTH) 2 Calcitonin (CT) inhibits
calcitriol. promotes release of Ca2+ from osteoclasts, decreasing
bone extracellular matrix into blood Ca2+ level.
ht
2+
blood and slows loss of Ca
in urine, increasing blood
2+
Ca level.
Q What are the primary target tissues for PTH, CT, and calcitriol?
W
Control of Secretion of Calcitonin and 4 PTH promotes resorption of bone extracellular matrix, which
releases Ca2+ into the blood and slows loss of Ca2+ in the urine,
Parathyroid Hormone raising the blood level of Ca2+.
ile
The blood calcium level directly controls the secretion of both calci- 5 PTH also stimulates the kidneys to synthesize calcitriol, the active
tonin and parathyroid hormone via negative feedback loops that do form of vitamin D.
not involve the pituitary gland (Figure 18.13): 6 Calcitriol stimulates increased absorption of Ca2+ from foods in
1 A higher-than-normal level of calcium ions (Ca2+) in the blood the gastrointestinal tract, which helps increase the blood level
stimulates parafollicular cells of the thyroid gland to release of Ca2+.
y,
more calcitonin. Table 18.7 summarizes control of secretion and the principal
2 Calcitonin inhibits the activity of osteoclasts, thereby decreasing actions of parathyroid hormone.
the blood Ca2+ level.
3 A lower-than-normal level of Ca2+ in the blood stimulates chief
cells of the parathyroid gland to release more PTH.
20
TA B LE 1 8 . 7 Summary of Parathyroid Gland Hormone
Chief cell
Parathyroid hormone Low blood Ca2+ levels stimulate secretion; Increases blood Ca2+ and Mg2+ levels and decreases
20
(PTH) from chief cells high blood Ca2+ levels inhibit secretion. blood HPO42− level; increases bone resorption
by osteoclasts; increases Ca2+ reabsorption and
HPO42− excretion by kidneys; promotes formation of
calcitriol (active form of vitamin D), which increases
rate of dietary Ca2+ and Mg2+ absorption.
612
adrenal glands differentiate into two structurally and functionally dis-

Checkpoint
tinct regions: a large, peripherally located adrenal cortex, comprising
16. How is secretion of parathyroid hormone regulated? 80–90% of the gland, and a small, centrally located adrenal medulla
C
17. In what ways are the actions of PTH and calcitriol similar? How
(Figure 18.14b). A connective tissue capsule covers the gland. The adre-
are they different? nal glands, like the thyroid gland, are highly vascularized.
The adrenal cortex produces steroid hormones that are essen-
op
tial for life. Complete loss of adrenocortical hormones leads to
death due to dehydration and electrolyte imbalances in a few days
to a week, unless hormone replacement therapy begins promptly.
18.9 Adrenal Glands The adrenal medulla produces three catecholamine hormones—
norepinephrine, epinephrine, and a small amount of dopamine.
OBJECTIVE
yr
Adrenal Cortex
• Describe the location, histology, hormones, and functions of the
adrenal glands. The adrenal cortex is subdivided into three zones, each of which
secretes different hormones (Figure 18.14d). The outer zone, just deep
to the connective tissue capsule, is the zona glomerulosa (glo-mer′-ū-
ig
-
The paired adrenal glands or suprarenal glands, one of which lies supe- LO-sa; zona = belt; glomerul- = little ball). Its cells, which are closely
rior to each kidney in the retroperitoneal space (Figure 18.14a), have a packed and arranged in spherical clusters and arched columns, secrete
flattened pyramidal shape. In an adult, each adrenal gland is 3–5 cm in hormones called mineralocorticoids (min′-er-al-ō-KOR-ti-koyds)
height, 2–3 cm in width, and a little less than 1 cm thick, with a mass of because they affect mineral homeostasis. The middle zone, or zona
ht
3.5–5 g, only half its size at birth. During embryonic development, the fasciculata (fa-sik′-ū-LA-ta; fascicul- = little bundle), is the widest of
FIGURE 18.14 Location, blood supply, and histology of the adrenal (suprarenal) glands.
The adrenal cortex secretes steroid hormones that are essential for life; the adrenal medulla
secretes norepinephrine and epinephrine.
W
Adrenal
glands
ile
Inferior phrenic
arteries
Kidney
Left adrenal gland
Celiac trunk
Right superior
y,
suprarenal arteries
Right adrenal
gland
Left middle suprarenal artery
Right middle
suprarenal artery
20
Right inferior Left inferior suprarenal artery
suprarenal artery Left suprarenal vein
Right renal artery Left renal artery
Right renal vein
Left renal vein
20
Superior mesenteric artery

Inferior vena cava Abdominal aorta
(a) Anterior view
613
18.9 Adrenal Glands 647
Capsule
Adrenal cortex:
Zona glomerulosa
C
Capsule
secretes
Adrenal mineralocorticoids,
cortex mainly aldosterone
Adrenal
op
medulla
Zona fasciculata
secretes
(b) Section through left adrenal gland glucocorticoids,
mainly cortisol
yr
Adrenal
gland Zona reticularis
secretes androgens
ig
Adrenal medulla
chromaffin cells secrete
epinephrine and
Kidney
norepinephrine (NE)
ht
Mark Nielsen LM 50x

(c) Anterior view of adrenal gland and kidney (d) Subdivisions of the adrenal gland
Q What is the position of the adrenal glands relative to the kidneys?

W
the three zones and consists of cells arranged in long, straight columns. 5 The level of renin in the blood increases.
The cells of the zona fasciculata secrete mainly glucocorticoids (gloo′- 6 Renin converts angiotensinogen (an′-jē-ō-ten-SIN-ō-jen), a
kō-KOR-ti-koyds), primarily cortisol, so named because they affect glu- plasma protein produced by the liver, into angiotensin I.
ile
cose homeostasis. The cells of the inner zone, the zona reticularis
7 Blood containing increased levels of angiotensin I circulates in
(re-tik′-ū-LAR-is; reticul- = network), are arranged in branching cords.
the body.
They synthesize small amounts of weak androgens (andro- = a man),
steroid hormones that have masculinizing effects. 8 As blood flows through capillaries, particularly those of the lungs,
the enzyme angiotensin-converting enzyme (ACE) converts
angiotensin I into the hormone angiotensin II.
Mineralocorticoids Aldosterone (al-DOS-ter-ōn) is the major
y,
mineralocorticoid. It regulates homeostasis of two mineral ions— 9 Blood level of angiotensin II increases.
namely, sodium ions (Na+) and potassium ions (K+)—and helps 10 Angiotensin II stimulates the adrenal cortex to secrete
adjust blood pressure and blood volume. Aldosterone also promotes aldosterone.
excretion of H+ in the urine; this removal of acids from the body can 11 Blood containing increased levels of aldosterone circulates to the
help prevent acidosis (blood pH below 7.35), which is discussed in kidneys.
Chapter 27.
20
12 In the kidneys, aldosterone increases reabsorption of Na+, which
in turn causes reabsorption of water by osmosis. As a result, less
Control of Aldosterone Secretion The renin– water is lost in the urine. Aldosterone also stimulates the kidneys
-
angiotensin–aldosterone (RAA) pathway (RE-nin an′-jē-ō-TEN-sin) to increase secretion of K+ and H+ into the urine.
controls secretion of aldosterone (Figure 18.15):
13 With increased water reabsorption by the kidneys, blood volume
1 Stimuli that initiate the renin–angiotensin–aldosterone pathway increases.
20
include dehydration, Na+ deficiency, or hemorrhage.
14 As blood volume increases, blood pressure increases to normal.
2 These conditions cause a decrease in blood volume.
15 Angiotensin II also stimulates contraction of smooth muscle in the
3 Decreased blood volume leads to decreased blood pressure. walls of arterioles. The resulting vasoconstriction of the arterioles
4 Lowered blood pressure stimulates certain cells of the kidneys, increases blood pressure and thus helps raise blood pressure to
called juxtaglomerular cells, to secrete the enzyme renin. normal.
614
FIGURE 18.15 Regulation of aldosterone secretion by the renin–angiotensin–aldosterone

(RAA) pathway.
C
Aldosterone helps regulate blood volume, blood pressure, and levels of Na+, K+, and H+ in the blood.
1 Dehydration,
op
+
Na deficiency,
or hemorrhage
2 Decrease in
blood volume 14
Blood pressure
increases until
yr
it returns to normal
4
3 Decrease in Juxtaglomerular
blood pressure cells of kidneys
15 13
Vasoconstriction Increased blood
ig
of arterioles volume
5 Increased renin
Adrenal
Liver
6 Angiotensinogen cortex
10 16
Increased
ht
+
K in
extracellular
8 7 Increased fluid
angiotensin I
11
ACE In kidneys, increased Na+
9 12 and water reabsorption
Increased Increased and increased secretion of
W
angiotensin II aldosterone K+ and H+ into urine
Lungs (ACE = angiotensin-
converting enzyme)
Q In what two ways can angiotensin II increase blood pressure, and what are its target tissues in each case?
ile
16 Besides angiotensin II, a second stimulator of aldosterone 3. Lipolysis. Glucocorticoids stimulate lipolysis (lī-POL-i-sis), the
+
secretion is an increase in the K concentration of blood (or breakdown of triglycerides and release of fatty acids from adipose
interstitial fluid). A decrease in the blood K+ level has the tissue into the blood.
opposite effect. 4. Resistance to stress. Glucocorticoids work in many ways to pro-
vide resistance to stress. The additional glucose supplied by the
y,
liver cells provides tissues with a ready source of ATP to combat
Glucocorticoids The glucocorticoids, which regulate
a range of stresses, including exercise, fasting, fright, tempera-
metabolism and resistance to stress, include cortisol (KOR-ti-sol;
ture extremes, high altitude, bleeding, infection, surgery, trauma,
also called hydrocortisone), corticosterone (kor′-ti-KOS-ter-ōn), and
and disease. Because glucocorticoids make blood vessels more
cortisone (KOR-ti-sōn). Of these three hormones secreted by the zona
sensitive to other hormones that cause vasoconstriction, they raise
fasciculata, cortisol is the most abundant, accounting for about 95%
blood pressure. This effect would be an advantage in cases of se-
20
of glucocorticoid activity.
vere blood loss, which causes blood pressure to drop.
Glucocorticoids have the following effects:
5. Anti-inflammatory effects. Glucocorticoids inhibit white blood
1. Protein breakdown. Glucocorticoids increase the rate of protein cells that participate in inflammatory responses. Unfortunately,
breakdown, mainly in muscle fibers, and thus increase the liberation glucocorticoids also retard tissue repair; as a result, they slow
of amino acids into the bloodstream. The amino acids may be used wound healing. Although high doses can cause severe mental
20
by body cells for synthesis of new proteins or for ATP production. disturbances, glucocorticoids are very useful in the treatment of
2. Glucose formation. On stimulation by glucocorticoids, liver cells chronic inflammatory disorders such as rheumatoid arthritis.
may convert certain amino acids or lactic acid to glucose, which 6. Depression of immune responses. High doses of glucocorticoids
neurons and other cells can use for ATP production. Such conver- depress immune responses. For this reason, glucocorticoids are
sion of a substance other than glycogen or another monosaccharide prescribed for organ transplant recipients to retard tissue rejection
into glucose is called gluconeogenesis (gloo′-ko-nē-ō-JEN-e-sis). by the immune system.
615
18.9 Adrenal Glands 649
FIGURE 18.16 Negative feedback regulation of glucocorticoid secretion. Control of Glucocorticoid Secretion Control of
glucocorticoid secretion occurs via a typical negative feedback
system (Figure 18.16). Low blood levels of glucocorticoids, mainly
C
A high level of CRH and a low level of glucocorticoids promote the
release of ACTH, which stimulates glucocorticoid secretion by the cortisol, stimulate neurosecretory cells in the hypothalamus to
adrenal cortex. secrete corticotropin-releasing hormone (CRH). CRH (together with
a low level of cortisol) promotes the release of ACTH from the anterior
op
pituitary. ACTH flows in the blood to the adrenal cortex, where it
stimulates glucocorticoid secretion. (To a much smaller extent,
STIMULUS
ACTH also stimulates secretion of aldosterone.) The discussion of
stress at the end of the chapter describes how the hypothalamus
Disrupts homeostasis also increases CRH release in response to a variety of physical and
by decreasing emotional stresses (see Section 18.14).
yr
CONTROLLED CONDITION Androgens In both males and females, the adrenal cortex
Glucocorticoid level in blood secretes small amounts of weak androgens. The major androgen
secreted by the adrenal gland is dehydroepiandrosterone (DHEA)
ig
(dē-hī-drō-ep′-ē-an-DROS-ter-ōn). After puberty in males, the
androgen testosterone is also released in much greater quantity by
RECEPTORS the testes. Thus, the amount of androgens secreted by the adrenal
gland in males is usually so low that their effects are insignificant.
Neurosecretory
cells in In females, however, adrenal androgens play important roles. They
ht
hypothalamus promote libido (sex drive) and are converted into estrogens (feminizing
– sex steroids) by other body tissues. After menopause, when ovarian
secretion of estrogens ceases, all female estrogens come from
conversion of adrenal androgens. Adrenal androgens also stimulate
Increased CRH and
Input growth of axillary and pubic hair in boys and girls and contribute to
decreased cortisol
the prepubertal growth spurt. Although control of adrenal androgen
W
secretion is not fully understood, the main hormone that stimulates
CONTROL CENTER its secretion is ACTH.
Corticotrophs
in anterior Return to
pituitary homeostasis when
the response brings
ile
glucocorticoid level in
blood back to normal Clinical Connection
Congenital Adrenal Hyperplasia

Output Increased ACTH
-
Congenital adrenal hyperplasia (CAH) (hī-per-PLA -zē-a) is a genetic dis-
order in which one or more enzymes needed for synthesis of cortisol are
y,
EFFECTORS absent. Because the cortisol level is low, secretion of ACTH by the ante-
rior pituitary is high due to lack of negative feedback inhibition. ACTH in
Cells of zona
fasciculata in turn stimulates growth and secretory activity of the adrenal cortex. As a
adrenal cortex result, both adrenal glands are enlarged. However, certain steps leading
to synthesis of cortisol are blocked. Thus, precursor molecules accumu-
late, and some of these are weak androgens that can undergo conversion
20
Secrete to testosterone. The result is virilism (VIR-i-lizm), or masculinization. In a
glucocorticoids
female, virile characteristics include growth of a beard, development of a
much deeper voice and a masculine distribution of body hair, growth of the
clitoris so it may resemble a penis, atrophy of the breasts, and increased
RESPONSE
muscularity that produces a masculine physique. In prepubertal males, the
Increased glucocorticoid
level in blood syndrome causes the same characteristics as in females, plus rapid devel-
opment of the male sexual organs and emergence of male sexual desires.
20
In adult males, the virilizing effects of CAH are usually completely obscured
by the normal virilizing effects of the testosterone secreted by the testes.
Q If a heart transplant patient receives prednisone As a result, CAH is often difficult to diagnose in adult males. Treatment
(a glucocorticoid) to help prevent rejection of the involves cortisol therapy, which inhibits ACTH secretion and thus reduces
transplanted tissue, will blood levels of ACTH and CRH production of adrenal androgens.
be high or low? Explain.
616
Adrenal Medulla Table 18.8 summarizes the hormones produced by the adrenal
glands, control of their secretion, and their principal actions.
The inner region of the adrenal gland, the adrenal medulla, is a mod-
C
ified sympathetic ganglion of the autonomic nervous system (ANS). It Checkpoint
develops from the same embryonic tissue as all other sympathetic
ganglia, but its cells, which lack axons, form clusters around large 18. How do the adrenal cortex and adrenal medulla compare with
regard to location and histology?
op
blood vessels. Rather than releasing a neurotransmitter, the cells of
the adrenal medulla secrete hormones. The hormone-producing 19. How is secretion of adrenal cortex hormones regulated?
-
cells, called chromaffin cells (KRO-maf-in; chrom- = color; -affin = 20. How is the adrenal medulla related to the autonomic nervous
affinity for; see Figure 18.14d), are innervated by sympathetic pregan- system?
glionic neurons of the ANS. Because the ANS exerts direct control over
the chromaffin cells, hormone release can occur very quickly.
yr
The two major hormones synthesized by the adrenal medulla are
epinephrine (ep′-i-NEF-rin) and norepinephrine (NE), also called adren-
aline and noradrenaline, respectively. The chromaffin cells of the adrenal
18.10 Pancreatic Islets
medulla secrete an unequal amount of these hormones—about 80% epi-
nephrine and 20% norepinephrine. The hormones of the adrenal medulla
ig
OBJECTIVE
intensify sympathetic responses that occur in other parts of the body.
• Describe the location, histology, hormones, and functions of the
Control of Secretion of Epinephrine and pancreatic islets.
Norepinephrine In stressful situations and during exercise,
ht
impulses from the hypothalamus stimulate sympathetic preganglionic
neurons, which in turn stimulate the chromaffin cells to secrete The pancreas (pan- = all; -creas = flesh) is both an endocrine gland
epinephrine and norepinephrine. These two hormones greatly augment and an exocrine gland. We discuss its endocrine functions here and
the fight-or-flight response that you learned about in Chapter 15. describe its exocrine functions in Chapter 24 in the coverage of the
By increasing heart rate and force of contraction, epinephrine and digestive system. A flattened organ that measures about 12.5–15 cm
norepinephrine increase the output of the heart, which increases (5–6 in.) in length, the pancreas is located in the curve of the duode-
W
blood pressure. They also increase blood flow to the heart, liver, num, the first part of the small intestine, and consists of a head, a body,
skeletal muscles, and adipose tissue; dilate airways to the lungs; and and a tail (Figure 18.17a). Roughly 99% of the exocrine cells of the pan-
increase blood levels of glucose and fatty acids. creas are arranged in clusters called acini (AS-i-nī). The acini produce
ile
TA B L E 1 8 . 8 Summary of Adrenal Gland Hormones
ADRENAL CORTEX HORMONES

Mineralocorticoids (mainly aldosterone) Increased blood K+ level and angiotensin II Increase blood levels of Na+ and water; decrease
from zona glomerulosa cells stimulate secretion. blood level of K+.
y,
Glucocorticoids (mainly cortisol) from ACTH stimulates release; corticotropin-releasing Increase protein breakdown (except in liver),
zona fasciculata cells hormone (CRH) promotes ACTH secretion in stimulate gluconeogenesis and lipolysis, provide
response to stress and low blood levels of resistance to stress, dampen inflammation,
glucocorticoids. depress immune responses.
Androgens (mainly ACTH stimulates secretion. Assist in early growth of axillary and pubic hair in
20
dehydroepiandrosterone, or DHEA) both sexes; in females, contribute to libido and
from zona reticularis cells are source of estrogens after menopause.
Adrenal
cortex
ADRENAL MEDULLA HORMONES

20
Epinephrine and norepinephrine from Sympathetic preganglionic neurons release Enhance effects of sympathetic division of
chromaffin cells acetylcholine, which stimulates secretion. autonomic nervous system (ANS) during stress.
Adrenal
medulla
617
18.10 Pancreatic Islets 651
FIGURE 18.17 Location, blood supply, and histology of the pancreas.

C
Pancreatic hormones regulate blood glucose level.
Pancreas Common hepatic artery

op
Kidney Abdominal aorta
Celiac trunk
Splenic artery
yr
Gastroduodenal artery
Dorsal pancreatic artery

Spleen
Anterior pancreaticoduodenal (elevated)
artery
ig
Duodenum of small intestine
Tail of pancreas
Body of pancreas
Inferior pancreatic artery
ht
Superior mesenteric artery
Inferior pancreaticoduodenal artery
Head of pancreas
(a) Anterior view
W
Blood capillary Exocrine

acinus
Pancreatic
ile
Alpha cell islet
(secretes glucagon) Beta
cell
Beta cell
Alpha
(secretes insulin)
cell
Delta cell
(secretes somatostatin)
y,
Acinus LM 200x
F cell (secretes
pancreatic polypeptide)
20
(b) Pancreatic islet and surrounding acini Pancreatic
Pancreas
duct
Mark Nielsen LM 40x
(c) Pancreatic islet and surrounding acini
Pancreatic
20
duct
Duodenum
(cut open)
Q Is the pancreas an exocrine gland or an

Mark Nielsen
endocrine gland?
(d) Anterior view of pancreas dissected
to reveal pancreatic duct
618
digestive enzymes, which flow into the gastrointestinal tract through a acids (lipogenesis); to slow the conversion of glycogen to glucose
network of ducts. Scattered among the exocrine acini are 1–2 million (glycogenolysis); and to slow the formation of glucose from lactic
-
tiny clusters of endocrine tissue called pancreatic islets (I -lets) or islets acid and amino acids (gluconeogenesis).
C
of Langerhans (LAHNG-er-hanz; Figure 18.17b, c). Abundant capillaries 7 As a result, blood glucose level falls.
serve both the exocrine and endocrine portions of the pancreas.
8 If blood glucose level drops below normal, low blood glucose
inhibits release of insulin (negative feedback) and stimulates
op
Cell Types in the Pancreatic Islets release of glucagon.
Although blood glucose level is the most important regulator of
Each pancreatic islet includes four types of hormone-secreting cells:
insulin and glucagon, several hormones and neurotransmitters also
1. Alpha or A cells constitute about 17% of pancreatic islet cells and regulate the release of these two hormones. In addition to the res-
secrete glucagon (GLOO-ka-gon). ponses to blood glucose level just described, glucagon stimulates
yr
insulin release directly; insulin has the opposite effect, suppressing
2. Beta or B cells constitute about 70% of pancreatic islet cells and
glucagon secretion. As blood glucose level declines and less insulin is
secrete insulin (IN-soo-lin).
secreted, the alpha cells of the pancreas are released from the inhibi-
3. Delta or D cells constitute about 7% of pancreatic islet cells and tory effect of insulin so they can secrete more glucagon. Indirectly, growth
secrete somatostatin (sō′-ma-tō-STAT-in). hormone (GH) and adrenocorticotropic hormone (ACTH) stimulate
ig
4. F cells constitute the remainder of pancreatic islet cells and secrete secretion of insulin because they act to elevate blood glucose.
pancreatic polypeptide.
The interactions of the four pancreatic hormones are complex FIGURE 18.18 Negative feedback regulation of the secretion of
and not completely understood. We do know that glucagon raises glucagon (blue arrows) and insulin (orange arrows).
ht
blood glucose level, and insulin lowers it. Somatostatin acts in a par-
acrine manner to inhibit both insulin and glucagon release from Low blood glucose stimulates release of glucagon; high blood glucose
neighboring beta and alpha cells. It may also act as a circulating hor- stimulates secretion of insulin.
mone to slow absorption of nutrients from the gastrointestinal tract.
In addition, somatostatin inhibits the secretion of growth hormone. 1 Low blood glucose 5 High blood glucose
(hypoglycemia) (hyperglycemia)
Pancreatic polypeptide inhibits somatostatin secretion, gallbladder stimulates alpha stimulates beta cells
contraction, and secretion of digestive enzymes by the pancreas. cells to secrete to secrete
W
Control of Secretion
of Glucagon and Insulin
ile
The principal action of glucagon is to increase blood glucose level

when it falls below normal. Insulin, on the other hand, helps lower
blood glucose level when it is too high. The level of blood glucose
controls secretion of glucagon and insulin via negative feedback Glucagon Insulin
(Figure 18.18):
y,
2 Glucagon acts on 6 Insulin acts on various
1 Low blood glucose level (hypoglycemia) stimulates secretion of liver cells to: body cells to:
glucagon from alpha cells of the pancreatic islets. convert glycogen accelerate facilitated
2 Glucagon acts on hepatocytes (liver cells) to accelerate the into glucose diffusion of glucose
form glucose from into cells
conversion of glycogen into glucose (glycogenolysis) and to lactic acid and speed conversion of
promote formation of glucose from lactic acid and certain amino certain amino acids glucose into glycogen
20
increase uptake of
acids (gluconeogenesis). amino acids and increase
3 As a result, hepatocytes release glucose into the blood more protein synthesis
3 Glucose released speed synthesis of fatty
rapidly, and blood glucose level rises. by liver cells raises
acids
blood glucose level
4 If blood glucose continues to rise, high blood glucose level to normal
(hyperglycemia) inhibits release of glucagon (negative feedback). 7 Blood glucose level falls
20
5 High blood glucose (hyperglycemia) stimulates secretion of
4 If blood glucose 8 If blood glucose continues
insulin by beta cells of the pancreatic islets. continues to rise, to fall, hypoglycemia
6 Insulin acts on various cells in the body to accelerate facilitated hyperglycemia inhibits inhibits release of insulin
release of glucagon
diffusion of glucose into cells; to speed conversion of glucose into
glycogen (glycogenesis); to increase uptake of amino acids by Q Does glycogenolysis increase or decrease blood glucose
cells and to increase protein synthesis; to speed synthesis of fatty level?
619
18.10 Pancreatic Islets 653
Insulin secretion is also stimulated by: Glucagon secretion is stimulated by:

• Acetylcholine, the neurotransmitter liberated from axon terminals • Increased activity of the sympathetic division of the ANS, as occurs
of parasympathetic vagus nerve fibers that innervate the pancre- during exercise
C
atic islets • A rise in blood amino acids if blood glucose level is low, which could
• The amino acids arginine and leucine, which would be present in the occur after a meal that contained mainly protein
blood at higher levels after a protein-containing meal Table 18.9 summarizes the hormones produced by the pancreas,
op
• Glucose-dependent insulinotropic peptide (GIP),* a hormone control of their secretion, and their principal actions.
released by enteroendocrine cells of the small intestine in
response to the presence of glucose in the gastrointestinal tract Checkpoint
Thus, digestion and absorption of food containing both carbo- 21. How are blood levels of glucagon and insulin controlled?
hydrates and proteins provide strong stimulation for insulin release. 22. What are the effects of exercise versus eating a carbohy-
yr
drate- and protein-rich meal on the secretion of insulin and
*GIP—previously called gastric inhibitory peptide—was renamed because at glucagon?
physiological concentration its inhibitory effect on stomach function is negligible.
ig
TA B LE 1 8 . 9 Summary of Pancreatic Islet Hormones
Glucagon from alpha cells of

pancreatic islets
ht
Decreased blood level of glucose, exercise, Raises blood glucose level by accelerating breakdown of
and mainly protein meals stimulate secretion; glycogen into glucose in liver (glycogenolysis), converting
somatostatin and insulin inhibit secretion. other nutrients into glucose in liver (gluconeogenesis), and
releasing glucose into blood.
W
Alpha cell
Insulin from beta cells of

pancreatic islets
Increased blood level of glucose, acetylcholine Lowers blood glucose level by accelerating transport
ile
(released by parasympathetic vagus nerve of glucose into cells, converting glucose into glycogen
fibers), arginine and leucine (two amino acids), (glycogenesis), and decreasing glycogenolysis and
glucagon, GIP, GH, and ACTH stimulate secretion; gluconeogenesis; increases lipogenesis and stimulates
somatostatin inhibits secretion. protein synthesis.
Beta cell
y,
Somatostatin from delta cells of
pancreatic islets
Pancreatic polypeptide inhibits secretion. Inhibits secretion of insulin and glucagon; slows absorption
of nutrients from gastrointestinal tract.
20
Delta cell
Pancreatic polypeptide from F

cells of pancreatic islets
Meals containing protein, fasting, exercise, Inhibits somatostatin secretion, gallbladder contraction, and
20
and acute hypoglycemia stimulate secretion; secretion of pancreatic digestive enzymes.
somatostatin and elevated blood glucose level
inhibit secretion.
F cell
620
18.11 Ovaries and Testes TABL E 18.10 Summary of Hormones of the Ovaries and Testes
HORMONE PRINCIPAL ACTIONS

C
OBJECTIVE OVARIAN HORMONES
Estrogens and Together with gonadotropic hormones
• Describe the location, hormones, and functions of the male and progesterone of anterior pituitary, regulate female
op
female gonads. reproductive cycle, maintain pregnancy,
prepare mammary glands for lactation, and
promote development and maintenance of
female secondary sex characteristics.
Gonads are the organs that produce gametes—sperm in males and
Ovary
oocytes in females. In addition to their reproductive function, the
gonads secrete hormones. The ovaries, paired oval bodies located in Relaxin (RLX) Increases flexibility of pubic symphysis
yr
the female pelvic cavity, produce several steroid hormones, including during pregnancy; helps dilate uterine cervix
two estrogens (estradiol and estrone) and progesterone. These female during labor and delivery.
sex hormones, along with follicle-stimulating hormone (FSH) and Inhibin Inhibits secretion of FSH from anterior
luteinizing hormone (LH) from the anterior pituitary, regulate the men- pituitary.
strual cycle, maintain pregnancy, and prepare the mammary glands for TESTICULAR HORMONES
ig
lactation. They also promote enlargement of the breasts and widening Testosterone Stimulates descent of testes before birth;
of the hips at puberty, and help maintain these female secondary sex regulates sperm production; promotes
development and maintenance of male
characteristics. The ovaries also produce inhibin, a protein hormone
secondary sex characteristics.
that inhibits secretion of FSH. During pregnancy, the ovaries and pla-
ht
centa produce a peptide hormone called relaxin (RLX), which increases Testis
the flexibility of the pubic symphysis during pregnancy and helps dilate
Inhibin Inhibits secretion of FSH from anterior
the uterine cervix during labor and delivery. These actions help ease the
pituitary.
baby’s passage by enlarging the birth canal.
The male gonads, the testes, are oval glands that lie in the scro-
tum. The main hormone produced and secreted by the testes is
testosterone, an androgen or male sex hormone. Testosterone stim-
W
midline (see Figure 18.1). Part of the epithalamus, it is positioned
ulates descent of the testes before birth, regulates production of
between the two superior colliculi, has a mass of 0.1–0.2 g, and is
sperm, and stimulates the development and maintenance of male
covered by a capsule formed by the pia mater. The gland consists
secondary sex characteristics, such as beard growth and deepening of
of masses of neuroglia and secretory cells called pinealocytes
the voice. The testes also produce inhibin, which inhibits secretion of
(pin-ē-AL-ō-sīts).
ile
FSH. The detailed structure of the ovaries and testes and the specific
The pineal gland secretes melatonin, an amine hormone de-
roles of sex hormones are discussed in Chapter 28.
rived from serotonin. Melatonin appears to contribute to the setting
Table 18.10 summarizes the hormones produced by the ovaries
of the body’s biological clock, which is controlled by the suprachias-
and testes and their principal actions.
matic nucleus of the hypothalamus. As more melatonin is liberated
during darkness than in light, this hormone is thought to promote
Checkpoint
y,
sleepiness. In response to visual input from the eyes (retina), the
23. Why are the ovaries and testes classified as endocrine glands suprachiasmatic nucleus stimulates sympathetic postganglionic
as well as reproductive organs? neurons of the superior cervical ganglion, which in turn stimulate the
pinealocytes of the pineal gland to secrete melatonin in a rhythmic
pattern, with low levels of melatonin secreted during the day and sig-
nificantly higher levels secreted at night. During sleep, plasma levels
Pineal Gland and Thymus
20
18.12 of melatonin increase tenfold and then decline to a low level again
before awakening. Small doses of melatonin given orally can induce
sleep and reset daily rhythms, which might benefit workers whose
OBJECTIVES shifts alternate between daylight and nighttime hours. Melatonin
also is a potent antioxidant that may provide some protection
• Describe the location, histology, hormone, and functions of the against damaging oxygen free radicals.
20
pineal gland. In animals that breed during specific seasons, melatonin in-
• Describe the role of the thymus in immunity. hibits reproductive functions, but it is unclear whether melatonin
influences human reproductive function. Melatonin levels are
higher in children and decline with age into adulthood, but there
-
The pineal gland (PI N-ē-al = pinecone shape) is a small endocrine is no evidence that changes in melatonin secretion correlate with
gland attached to the roof of the third ventricle of the brain at the the onset of puberty and sexual maturation. Nevertheless,
621
18.13 Other Endocrine Tissues and Organs, Eicosanoids, and Growth Factors 655
because melatonin causes atrophy of the gonads in several ani- Eicosanoids

mal species, the possibility of adverse effects on human repro-
duction must be studied before its use to reset daily rhythms can Two families of eicosanoid molecules—the prostaglandins (PGs)
C
-
be recommended. (pros′-ta-GLAN-dins) and the leukotrienes (LTs) (loo-kō-TRI -ēns)—
are found in virtually all body cells except red blood cells, where they
Clinical Connection act as local hormones (paracrines or autocrines) in response to chem-
op
ical or mechanical stimuli. They are synthesized by clipping a 20-
Seasonal Affective Disorder and Jet Lag carbon fatty acid called arachidonic acid (a-rak-i-DON-ik) from mem-
brane phospholipid molecules. From arachidonic acid, different enzy-
Seasonal affective disorder (SAD) is a type of depression that afflicts
matic reactions produce PGs or LTs. Thromboxane (TX) (throm-BOK-sān)
some people during the winter months, when day length is short. It is
is a modified PG that constricts blood vessels and promotes platelet
thought to be due, in part, to overproduction of melatonin. Full-spectrum
bright-light therapy—repeated doses of several hours of exposure to arti- activation. Appearing in the blood in minute quantities, eicosanoids
yr
ficial light as bright as sunlight—provides relief for some people. Three to are present only briefly due to rapid inactivation.
six hours of exposure to bright light also appears to speed recovery from jet
lag, the fatigue suffered by travelers who quickly cross several time zones.
Summary of Hormones Produced by Other
TABL E 18.11 Organs and Tissues That Contain Endocrine Cells
ig
The thymus is located behind the sternum between the lungs. HORMONE PRINCIPAL ACTIONS
Because of the role of the thymus in immunity, the details of its struc-
SKIN
ture and functions are discussed in Chapter 22. The hormones pro-
Cholecalciferol Plays a role in the synthesis of calcitriol, the
duced by the thymus—thymosin, thymic humoral factor (THF),
- active form of vitamin D.
ht
thymic factor (TF), and thymopoietin (thī-mō-poy-E-tin)—promote
the maturation of T cells (a type of white blood cell that destroys mi- GASTROINTESTINAL TRACT
crobes and foreign substances) and may retard the aging process. Gastrin Promotes secretion of gastric juice; increases
movements of the stomach.
Glucose-dependent Stimulates release of insulin by pancreatic
Checkpoint insulinotropic beta cells.
peptide (GIP)
24. What is the relationship between melatonin and sleep?
W
Secretin Stimulates secretion of pancreatic juice and
25. Which thymic hormones play a role in immunity? bile.
Cholecystokinin Stimulates secretion of pancreatic juice;
(CCK) regulates release of bile from gallbladder;
causes feeling of fullness after eating.
ile
18.13 Other Endocrine Tissues PLACENTA
Human chorionic Stimulates corpus luteum in ovary to continue
and Organs, Eicosanoids, gonadotropin production of estrogens and progesterone to
(hCG) maintain pregnancy.
and Growth Factors Estrogens and Maintain pregnancy; help prepare mammary
progesterone glands to secrete milk.
y,
Human chorionic Stimulates development of mammary glands
OBJECTIVES somatomam- for lactation.
motropin (hCS)
• Outline the functions of each of the hormones secreted by cells in KIDNEYS
tissues and organs other than endocrine glands. Renin Part of reaction sequence that raises blood
• Describe the actions of eicosanoids and growth factors. pressure by bringing about vasoconstriction
20
and secretion of aldosterone.
Erythropoietin (EPO) Increases rate of red blood cell formation.
Calcitriol* (active Aids in absorption of dietary calcium and
Hormones from Other Endocrine Tissues form of vitamin D) phosphorus
and Organs HEART
Atrial natriuretic Decreases blood pressure.
20
As you learned at the beginning of this chapter, cells in organs other peptide (ANP)
than those usually classified as endocrine glands have an endocrine
ADIPOSE TISSUE
function and secrete hormones. You learned about several of these in
this chapter: the hypothalamus, thymus, pancreas, ovaries, and testes. Leptin Suppresses appetite; may increase FSH and LH
activity.
Table 18.11 provides an overview of these organs and tissues and
their hormones and actions. *Synthesis begins in the skin, continues in the liver, and ends in the kidneys.
622
To exert their effects, eicosanoids bind to receptors on target-cell

TABL E 18.12 Summary of Selected Growth Factors
plasma membranes and stimulate or inhibit the synthesis of second
messengers such as cyclic AMP. Leukotrienes stimulate chemotaxis GROWTH FACTOR COMMENT
C
(attraction to a chemical stimulus) of white blood cells and mediate
Epidermal growth Produced in submaxillary (salivary) glands;
inflammation. The prostaglandins alter smooth muscle contraction, factor (EGF) stimulates proliferation of epithelial cells,
glandular secretions, blood flow, reproductive processes, platelet fibroblasts, neurons, and astrocytes;
op
function, respiration, nerve impulse transmission, lipid metabolism, suppresses some cancer cells and secretion of
and immune responses. They also have roles in promoting inflamma- gastric juice by stomach.
tion and fever, and in intensifying pain. Platelet-derived Produced in blood platelets; stimulates
growth factor proliferation of neuroglia, smooth muscle
Clinical Connection (PDGF) fibers, and fibroblasts; appears to have
role in wound healing; may contribute to
atherosclerosis development.
yr
Nonsteroidal Anti-inflammatory Drugs
Fibroblast growth Found in pituitary gland and brain;
In 1971, scientists solved the long-standing puzzle of how aspirin works. factor (FGF) stimulates proliferation of many cells derived
Aspirin and related nonsteroidal anti-inflammatory drugs (NSAIDs), from embryonic mesoderm (fibroblasts,
such as ibuprofen (Motrin®), inhibit cyclooxygenase (COX), a key enzyme adrenocortical cells, smooth muscle fibers,
involved in prostaglandin synthesis. NSAIDs are used to treat a wide variety chondrocytes, and endothelial cells);
ig
stimulates formation of new blood vessels
of inflammatory disorders, from rheumatoid arthritis to tennis elbow. The
(angiogenesis).
success of NSAIDs in reducing fever, pain, and inflammation shows how
prostaglandins contribute to these woes. Nerve growth Produced in submandibular (salivary) glands
factor (NGF) and hippocampus of brain; stimulates growth
of ganglia in embryo; maintains sympathetic
ht
nervous system; stimulates hypertrophy and
differentiation of neurons.
Growth Factors
Tumor angiogenesis Produced by normal and tumor cells;
Several of the hormones we have described—insulinlike growth factor, factors (TAFs) stimulate growth of new capillaries, organ
thymosin, insulin, thyroid hormones, growth hormone, and prolactin— regeneration, and wound healing.
stimulate cell growth and division. In addition, several more recently Transforming growth Produced by various cells as separate
factors (TGFs) molecules: TGF-alpha has activities similar
discovered hormones called growth factors play important roles in
W
to epidermal growth factor; TGF-beta inhibits
tissue development, growth, and repair. Growth factors are mitogenic proliferation of many cell types.
substances—they cause growth by stimulating cell division. Many
growth factors act locally, as autocrines or paracrines.
A summary of sources and actions of six important growth fac-
ile
tors is presented in Table 18.12. wound or surgery, or a strong emotional reaction. The responses to
stressors may be pleasant or unpleasant, and they vary among people
Checkpoint and even within the same person at different times.
Your body’s homeostatic mechanisms attempt to counteract
26. What hormones are secreted by the gastrointestinal tract, stress. When they are successful, the internal environment remains
placenta, kidneys, skin, adipose tissue, and heart? within normal physiological limits. If stress is extreme, unusual, or long
y,
27. What are some functions of prostaglandins, leukotrienes, and lasting, the normal mechanisms may not be enough. In 1936, Hans
growth factors? Selye, a pioneer in stress research, showed that a variety of stressful
conditions or noxious agents elicit a similar sequence of bodily changes.
These changes, called the stress response or general adaptation syn-
drome (GAS), are controlled mainly by the hypothalamus. The stress
18.14 The Stress Response response occurs in three stages: (1) an initial fight-or-flight response,
20
(2) a slower resistance reaction, and eventually (3) exhaustion.
OBJECTIVE
The Fight-or-Flight Response
• Describe how the body responds to stress.
The fight-or-flight response, initiated by nerve impulses from the
20
hypothalamus to the sympathetic division of the autonomic nervous
It is impossible to remove all of the stress from our everyday lives. system (ANS), including the adrenal medulla, quickly mobilizes the
Some stress, called eustress, prepares us to meet certain challenges body’s resources for immediate physical activity (Figure 18.19a). It
and thus is helpful. Other stress, called distress, is harmful. Any brings huge amounts of glucose and oxygen to the organs that are
stimulus that produces a stress response is called a stressor. A stressor most active in warding off danger: the brain, which must become
may be almost any disturbance of the human body—heat or cold, envi- highly alert; the skeletal muscles, which may have to fight off an
ronmental poisons, toxins given off by bacteria, heavy bleeding from a attacker or flee; and the heart, which must work vigorously to pump
623
18.14 The Stress Response 657
enough blood to the brain and muscles. During the fight-or-flight angiotensin–aldosterone pathway (see Figure 18.15). Aldosterone
response, nonessential body functions such as digestive, urinary, and causes the kidneys to retain Na+, which leads to water retention and
reproductive activities are inhibited. Reduction of blood flow to the elevated blood pressure. Water retention also helps preserve body
C
kidneys promotes release of renin, which sets into motion the renin– fluid volume in the case of severe bleeding.
FIGURE 18.19 Responses to stressors during the stress response. Red arrows (hormonal
op
responses) and green arrows (neural responses) in (a) indicate immediate fight-or-flight reactions; black
arrows in (b) indicate long-term resistance reactions.
Stressors stimulate the hypothalamus to initiate the stress response through the fight-or-flight
response and the resistance reaction.
STRESSORS
yr
Key:
stimulate
CRH = Corticotropin-releasing hormone
ACTH = Adrenocorticotropic hormone
GHRH = Growth hormone–releasing hormone
CRH Hypothalamus GH = Growth hormone
Nerve
GHRH TRH = Thyrotropin-releasing hormone
ig
impulses
TRH TSH = Thyroid-stimulating hormone
Sympathetic centers
in spinal cord
Anterior
pituitary
ht
TSH
GH
ACTH
Sympathetic nerves
ACTH GH TSH
W
Adrenal
medulla
Liver Thyroid
Adrenal gland
cortex
ile
Visceral effectors
Cortisol IGFs Thyroid hormones

(T3 and T4)
Epinephrine
and
y,
norepinephrine Stress responses Stress responses Stress Stress
Lipolysis responses responses
1. Increased heart rate Gluconeogenesis Lipolysis Increased use
and force of heartbeat Protein catabolism Glycogenolysis of glucose to
Supplement
and prolong 2. Constriction of blood Sensitized blood vessels produce ATP
“fight-or-flight” vessels of most Reduced inflammation
responses viscera and skin
3. Dilation of blood
20
vessels of heart,
lungs, brain, and
skeletal muscles
4. Contraction of spleen
5. Conversion of glycogen
into glucose in liver
6. Sweating
20
7. Dilation of airways
8. Decrease in digestive
activities
9. Water retention and
elevated blood pressure
(a) Fight-or-flight responses (b) Resistance reaction

Q What is the basic difference between the stress response and homeostasis?
624
The Resistance Reaction important link between stress and immunity. One action of interleu-
kin-1 is to stimulate secretion of ACTH, which in turn stimulates the
The second stage in the stress response is the resistance reaction production of cortisol. Not only does cortisol provide resistance to
C
(Figure 18.19b). Unlike the short-lived fight-or-flight response, which stress and inflammation, but it also suppresses further production of
is initiated by nerve impulses from the hypothalamus, the resistance interleukin-1. Thus, the immune system turns on the stress response,
reaction is initiated in large part by hypothalamic releasing hormones and the resulting cortisol then turns off one immune system mediator.
op
and is a longer-lasting response. The hormones involved are cortico- This negative feedback system keeps the immune response in check
tropin-releasing hormone (CRH), growth hormone–releasing hor- once it has accomplished its goal. Because of this activity, cortisol and
mone (GHRH), and thyrotropin-releasing hormone (TRH). other glucocorticoids are used as immunosuppressive drugs for organ
CRH stimulates the anterior pituitary to secrete ACTH, which in transplant recipients.
turn stimulates the adrenal cortex to increase release of cortisol. Cor-
tisol then stimulates gluconeogenesis by liver cells, breakdown of tri- Clinical Connection
yr
glycerides into fatty acids (lipolysis), and catabolism of proteins into
amino acids. Tissues throughout the body can use the resulting glu- Post-Traumatic Stress Disorder
cose, fatty acids, and amino acids to produce ATP or to repair dam-
Post-traumatic stress disorder (PTSD) is an anxiety disorder that may
aged cells. Cortisol also reduces inflammation.
develop in an individual who has experienced, witnessed, or learned about
A second hypothalamic releasing hormone, GHRH, causes the
ig
a physically or psychologically distressing event. The immediate cause
anterior pituitary to secrete growth hormone (GH). Acting via insulin- of PTSD appears to be the specific stressors associated with the events.
like growth factors, GH stimulates lipolysis and glycogenolysis, the Among the stressors are terrorism, hostage taking, imprisonment, military
breakdown of glycogen to glucose, in the liver. A third hypothalamic duty, serious accidents, torture, sexual or physical abuse, violent crimes,
releasing hormone, TRH, stimulates the anterior pituitary to secrete school shootings, massacres, and natural disasters. In the United States,
ht
thyroid-stimulating hormone (TSH). TSH promotes secretion of thy- PTSD affects 10% of females and 5% of males. Symptoms of PTSD include
roid hormones, which stimulate the increased use of glucose for ATP reexperiencing the event through nightmares or flashbacks; avoidance of
production. The combined actions of GH and TSH supply additional any activity, person, place, or event associated with the stressors; loss of
ATP for metabolically active cells throughout the body. interest and lack of motivation; poor concentration; irritability; and insom-
The resistance stage helps the body continue fighting a stressor nia. Treatment may include the use of antidepressants, mood stabilizers,
and antianxiety and antipsychotic agents.
long after the fight-or-flight response dissipates. This is why your
heart continues to pound for several minutes even after the stressor is
W
removed. Generally, it is successful in seeing us through a stressful
episode, and our bodies then return to normal. Occasionally, how-
ever, the resistance stage fails to combat the stressor, and the body Checkpoint
moves into the state of exhaustion.
ile
28. What is the central role of the hypothalamus during stress?
29. What body reactions occur during the fight-or-flight response,
Exhaustion the resistance reaction, and exhaustion?
The resources of the body may eventually become so depleted that 30. What is the relationship between stress and immunity?
they cannot sustain the resistance stage, and exhaustion ensues.
Prolonged exposure to high levels of cortisol and other hormones
y,
involved in the resistance reaction causes wasting of muscle, suppres-
sion of the immune system, ulceration of the gastrointestinal tract, 18.15 Development of
and failure of pancreatic beta cells. In addition, pathological changes
may occur because resistance reactions persist after the stressor has the Endocrine
been removed.
System
20
Stress and Disease

OBJECTIVE
Although the exact role of stress in human diseases is not known, it is
clear that stress can lead to particular diseases by temporarily inhibit- • Describe the development of endocrine glands.
ing certain components of the immune system. Stress-related disor-
20
ders include gastritis, ulcerative colitis, irritable bowel syndrome,
hypertension, asthma, rheumatoid arthritis (RA), migraine head- The development of the endocrine system is not as localized as the
aches, anxiety, and depression. People under stress are at a greater development of other systems because, as you have already learned,
risk of developing chronic disease or dying prematurely. endocrine organs are distributed throughout the body.
Interleukin-1, a substance secreted by macrophages of the About 3 weeks after fertilization, the pituitary gland (hypophysis)
immune system (see the discussion of ACTH in Section 18.6), is an begins to develop from two different regions of the ectoderm. The
625
Chapter Review 665
Chapter Review
C
Review 18.6 Hypothalamus and Pituitary Gland

1. The hypothalamus is the major integrating link between the nervous and
op
Introduction endocrine systems. The hypothalamus and pituitary gland regulate virtually
1. Hormones regulate the activity of smooth muscle, cardiac muscle, and all aspects of growth, development, metabolism, and homeostasis. The pi-
some glands; alter metabolism; spur growth and development; influence tuitary gland is located in the hypophyseal fossa and is divided into two main
reproductive processes; and participate in circadian (daily) rhythms. portions: the anterior pituitary (glandular portion) and the posterior pituitary
(nervous portion).
18.1 Comparison of Control by the Nervous and 2. Secretion of anterior pituitary hormones is stimulated by releasing hor-
yr
Endocrine Systems mones and suppressed by inhibiting hormones from the hypothalamus.
1. The nervous system controls homeostasis through nerve impulses and neu- 3. The blood supply to the anterior pituitary is from the superior hypophyseal
rotransmitters, which act locally and quickly. The endocrine system uses hor- arteries. Hypothalamic releasing and inhibiting hormones enter the primary
mones, which act more slowly in distant parts of the body. (See Table 18.1.) plexus and flow to the secondary plexus in the anterior pituitary by the hypo-
2. The nervous system controls neurons, muscle cells, and glandular cells; the physeal portal veins.
ig
endocrine system regulates virtually all body cells. 4. The anterior pituitary consists of somatotrophs that produce growth hor-
mone (GH), lactotrophs that produce prolactin (PRL), corticotrophs that
18.2 Endocrine Glands secrete adrenocorticotropic hormone (ACTH) and melanocyte-stimulating
1. Exocrine glands (sudoriferous, sebaceous, mucous, and digestive) secrete hormone (MSH), thyrotrophs that secrete thyroid-stimulating hormone (TSH),
ht
their products through ducts into body cavities or onto body surfaces. Endo- and gonadotrophs that synthesize follicle-stimulating hormone (FSH) and
crine glands secrete hormones into interstitial fluid. Then, the hormones luteinizing hormone (LH). (See Tables 18.3 and 18.4.)
diffuse into the blood. 5. Growth hormone (GH) stimulates body growth through insulinlike growth
2. The endocrine system consists of endocrine glands (pituitary, thyroid, factors (IGFs). Secretion of GH is inhibited by GHIH (growth hormone–inhibiting
parathyroid, adrenal, and pineal glands) and other hormone-secreting tissues hormone, or somatostatin) and promoted by GHRH (growth hormone–releasing
(hypothalamus, thymus, pancreas, ovaries, testes, kidneys, stomach, liver, hormone).
small intestine, skin, heart, adipose tissue, and placenta). 6. TSH regulates thyroid gland activities. Its secretion is stimulated by TRH
W
(thyrotropin-releasing hormone) and suppressed by GHIH.
18.3 Hormone Activity
7. FSH and LH regulate the activities of the gonads—ovaries and testes. Their
1. Hormones affect only specific target cells that have receptors to recognize secretion is controlled by GnRH (gonadotropin-releasing hormone).
(bind) a given hormone. The number of hormone receptors may decrease
8. Prolactin (PRL) helps initiate milk secretion. Prolactin-inhibiting hormone
(down-regulation) or increase (up-regulation).
ile
(PIH) suppresses secretion of PRL; prolactin-releasing hormone (PRH) stimu-
2. Circulating hormones enter the bloodstream; local hormones (paracrines lates PRL secretion.
and autocrines) act locally on neighboring cells.
9. ACTH regulates the activities of the adrenal cortex and is controlled by CRH
3. Chemically, hormones are either lipid-soluble (steroids, thyroid hormones, (corticotropin-releasing hormone). Dopamine inhibits secretion of MSH.
and nitric oxide) or water-soluble (amines; peptides, proteins, and glycopro-
10. The posterior pituitary contains axon terminals of neurosecretory cells
teins; and eicosanoids). (See Table 18.2.)
whose cell bodies are in the hypothalamus. Hormones made by the hypothal-
y,
4. Water-soluble hormone molecules circulate in the watery blood plasma in amus and stored in the posterior pituitary are oxytocin (OT), which stimulates
a “free” form (not attached to plasma proteins); most lipid-soluble hormones contraction of the uterus and ejection of milk from the breasts, and antidiu-
are bound to transport proteins synthesized by the liver. retic hormone (ADH), which stimulates water reabsorption by the kidneys and
constriction of arterioles. (See Table 18.5.) Oxytocin secretion is stimulated by
18.4 Mechanisms of Hormone Action uterine stretching and suckling during nursing; ADH secretion is controlled by
1. Lipid-soluble steroid hormones and thyroid hormones affect cell function osmotic pressure of the blood and blood volume.
20
by altering gene expression.
18.7 Thyroid Gland
2. Water-soluble hormones alter cell function by activating plasma membrane
receptors, which elicit production of a second messenger that activates 1. The thyroid gland is located inferior to the larynx.
various enzymes inside the cell. 2. It consists of thyroid follicles composed of follicular cells, which secrete the
3. Hormonal interactions can have three types of effects: permissive, syner- thyroid hormones thyroxine (T4) and triiodothyronine (T3), and parafollicular
gistic, or antagonistic. cells, which secrete calcitonin (CT).
20
3. Thyroid hormones are synthesized from iodine and tyrosine within thy-
18.5 Homeostatic Control of Hormone Secretion roglobulin (TGB). They are transported in the blood bound to plasma proteins,
1. Hormone secretion is controlled by signals from the nervous system, mostly thyroxine-binding globulin (TBG).
chemical changes in blood, and other hormones. 4. Secretion is controlled by TRH from the hypothalamus and thyroid-
2. Negative feedback systems regulate the secretion of many hormones. stimulating hormone (TSH) from the anterior pituitary.
626
5. Thyroid hormones regulate oxygen use and metabolic rate, cellular metab- 2. The pineal gland secretes melatonin, which contributes to setting the
olism, and growth and development. body’s biological clock (controlled in the suprachiasmatic nucleus). During
6. Calcitonin (CT) can lower the blood level of calcium ions (Ca2+) and pro- sleep, plasma levels of melatonin increase.
C
mote deposition of Ca2+ into bone matrix. Secretion of CT is controlled by the 3. The thymus secretes several hormones related to immunity.
Ca2+ level in the blood. (See Table 18.6.) 4. Thymosin, thymic humoral factor (THF), thymic factor (TF), and thymopoi-
etin promote the maturation of T cells.
18.8 Parathyroid Glands
op
1. The parathyroid glands are embedded in the posterior surfaces of the 18.13 Other Endocrine Tissues and Organs, Eicosanoids,
lateral lobes of the thyroid gland. They consist of chief cells and oxyphil cells. and Growth Factors
2. Parathyroid hormone (PTH) regulates the homeostasis of calcium, 1. Body tissues other than those normally classified as endocrine glands con-
magnesium, and phosphate ions by increasing blood calcium and magnesium tain endocrine tissue and secrete hormones; they include the gastrointestinal
levels and decreasing blood phosphate levels. PTH secretion is controlled by tract, placenta, kidneys, skin, and heart. (See Table 18.11.)
the level of calcium in the blood. (See Table 18.7.)
yr
2. Prostaglandins and leukotrienes are eicosanoids that act as local hormones
18.9 Adrenal Glands in most body tissues.
1. The adrenal glands are located superior to the kidneys. They consist of an 3. Growth factors are local hormones that stimulate cell growth and division.
outer adrenal cortex and inner adrenal medulla. (See Table 18.12.)
2. The adrenal cortex is divided into a zona glomerulosa, a zona fasciculata,
ig
18.14 The Stress Response
and a zona reticularis; the adrenal medulla consists of chromaffin cells and
1. Productive stress is termed eustress, and harmful stress is termed distress.
large blood vessels.
2. If stress is extreme, it triggers the stress response (general adaptation syn-
3. Cortical secretions include mineralocorticoids, glucocorticoids, and androgens.
drome), which occurs in three stages: the fight-or-flight response, resistance
4. Mineralocorticoids (mainly aldosterone) increase sodium and water reab- reaction, and exhaustion.
ht
sorption and decrease potassium reabsorption. Secretion is controlled by the
3. The stimuli that produce the stress response are called stressors. Stressors
renin–angiotensin–aldosterone (RAA) pathway and by K+ level in the blood.
include surgery, poisons, infections, fever, and strong emotional responses.
5. Glucocorticoids (mainly cortisol) promote protein breakdown, gluconeo-
4. The fight-or-flight response is initiated by nerve impulses from the hypo-
genesis, and lipolysis; help resist stress; and serve as anti-inflammatory sub-
thalamus to the sympathetic division of the autonomic nervous system and
stances. Their secretion is controlled by ACTH.
the adrenal medulla. This response rapidly increases circulation, promotes
6. Androgens secreted by the adrenal cortex stimulate growth of axillary and ATP production, and decreases nonessential activities.
W
pubic hair, aid the prepubertal growth spurt, and contribute to libido.
5. The resistance reaction is initiated by releasing hormones secreted by the
7. The adrenal medulla secretes epinephrine and norepinephrine (NE), which hypothalamus, most importantly CRH, TRH, and GHRH. Resistance reactions
are released during stress and produce effects similar to sympathetic are longer lasting and accelerate breakdown reactions to provide ATP for
responses. (See Table 18.8.) counteracting stress.
ile
18.10 Pancreatic Islets 6. Exhaustion results from depletion of body resources during the resistance
stage.
1. The pancreas lies in the curve of the duodenum. It has both endocrine and
exocrine functions. 7. Stress may trigger certain diseases by inhibiting the immune system. An
important link between stress and immunity is interleukin-l, produced by
2. The endocrine portion consists of pancreatic islets or islets of Langerhans,
macrophages; it stimulates secretion of ACTH.
made up of four types of cells: alpha, beta, delta, and F cells.
3. Alpha cells secrete glucagon, beta cells secrete insulin, delta cells secrete 18.15 Development of the Endocrine System
y,
somatostatin, and F cells secrete pancreatic polypeptide. 1. The development of the endocrine system is not as localized as in other
4. Glucagon increases blood glucose level; insulin decreases blood glucose systems because endocrine organs develop in widely separated parts of the
level. Secretion of both hormones is controlled by the level of glucose in the embryo.
blood. (See Table 18.9.) 2. The pituitary gland, adrenal medulla, and pineal gland develop from
ectoderm; the adrenal cortex develops from mesoderm; and the thyroid
18.11 Ovaries and Testes
20
gland, parathyroid glands, pancreas, and thymus develop from endoderm.
1. The ovaries are located in the pelvic cavity and produce estrogens, pro-
gesterone, and inhibin. These sex hormones govern the development and main- 18.16 Aging and the Endocrine System
tenance of female secondary sex characteristics, reproductive cycles, pregnancy, 1. Although some endocrine glands shrink as we get older, their performance
lactation, and normal female reproductive functions. (See Table 18.10.) may or may not be compromised.
2. The testes lie inside the scrotum and produce testosterone and inhibin. These 2. Production of growth hormone, thyroid hormones, cortisol, aldosterone,
sex hormones govern the development and maintenance of male secondary sex
20
and estrogens decreases with advancing age.
characteristics and normal male reproductive functions. (See Table 18.10.)
3. With aging, the blood levels of TSH, LH, FSH, and PTH rise.
18.12 Pineal Gland and Thymus 4. The pancreas releases insulin more slowly with age, and receptor sensitivity
1. The pineal gland is attached to the roof of the third ventricle of the brain. to glucose declines.
It consists of secretory cells called pinealocytes, neuroglia, and endings of 5. After puberty, thymus size begins to decrease, and thymic tissue is replaced
sympathetic postganglionic axons. by adipose and areolar connective tissue.
627
Answers to Figure Questions 667
Critical Thinking Questions

C
1. Amanda hates her new student ID photo. Her hair looks dry, the extra weight monitored. After TSH injection, her T4 levels rise. Does Amanda have prob-
that she’s gained shows, and her neck looks fat. In fact, there’s an odd butterfly- lems with her pituitary or with her thyroid gland? How did you come to your
op
shaped swelling across the front of her neck, under her chin. Amanda’s also conclusion?
been feeling very tired and mentally “dull” lately, but she figures all new A&P 3. Mr. Hernandez visited his doctor complaining that he is constantly thirsty
students feel that way. Should she visit the clinic or just wear turtlenecks? and is “in the bathroom day and night” relieving his bladder. The doctor or-
2. Amanda (from question 1 above) goes to the clinic and blood is drawn. The dered blood and urine tests to check for glucose and ketones, which were all
results show that her T4 levels are low and her TSH levels are low. Later she negative. What is the doctor’s diagnosis of Mr. Hernandez, and what gland(s)
is given a TSH stimulation test in which TSH is injected and the T4 levels are or organ(s) is(are) involved?
yr
Answers to Figure Questions

ig
18.1 Secretions of endocrine glands diffuse into interstitial fluid and then into 18.11 Lack of iodine in the diet → diminished production of T3 and T4 → in-
the blood; exocrine secretions flow into ducts that lead into body cavities or creased release of TSH → growth (enlargement) of the thyroid gland → goiter.
to the body surface. 18.12 Parafollicular cells of the thyroid gland secrete calcitonin; chief (princi-
ht
18.2 In the stomach, histamine is a paracrine because it acts on nearby pal) cells of the parathyroid gland secrete PTH.
parietal cells without entering the blood. 18.13 Target tissues for PTH are bones and the kidneys; target tissue for CT
18.3 The receptor–hormone complex alters gene expression by turning is bone; target tissue for calcitriol is the GI tract.
specific genes of nuclear DNA on or off. 18.14 The adrenal glands are superior to the kidneys in the retroperitoneal
18.4 Cyclic AMP is termed a second messenger because it translates the space.
presence of the first messenger, the water-soluble hormone, into a response 18.15 Angiotensin II acts to constrict blood vessels by causing contraction of
inside the cell.
W
vascular smooth muscle, and it stimulates secretion of aldosterone (by zona
18.5 The hypophyseal portal veins carry blood from the median eminence of glomerulosa cells of the adrenal cortex), which in turn causes the kidneys to
the hypothalamus, where hypothalamic releasing and inhibiting hormones conserve water and thereby increase blood volume.
are secreted, to the anterior pituitary, where these hormones act. 18.16 A transplant recipient who takes prednisone will have low blood levels
18.6 Thyroid hormones suppress secretion of TSH by thyrotrophs and of TRH of ACTH and CRH due to negative feedback suppression of the anterior pitui-
ile
by hypothalamic neurosecretory cells; gonadal hormones suppress secretion of tary and hypothalamus by the prednisone.
FSH and LH by gonadotrophs and of GnRH by hypothalamic neurosecretory cells. 18.17 The pancreas is both an endocrine and an exocrine gland.
18.7 Excess levels of GH would cause hyperglycemia. 18.18 Glycogenolysis is the conversion of glycogen into glucose and therefore
18.8 Functionally, both the hypothalamic–hypophyseal tract and the hypo- it increases blood glucose level.
physeal portal veins carry hypothalamic hormones to the pituitary gland. 18.19 Homeostasis maintains controlled conditions typical of a normal inter-
Structurally, the tract is composed of axons of neurons that extend from the nal environment; the stress response resets controlled conditions at a differ-
y,
hypothalamus to the posterior pituitary; the portal veins are blood vessels ent level to cope with various stressors.
that extend from the hypothalamus to the anterior pituitary.
18.20 The adrenal cortex of the adrenal gland is derived from mesoderm,
18.9 Follicular cells secrete T3 and T4, also known as thyroid hormones. Para-
while the adrenal medulla of the adrenal gland is derived from ectoderm.
follicular cells secrete calcitonin.
18.10 The storage form of thyroid hormones is thyroglobulin. 18.21 Antibodies that mimic the action of TSH are produced in Graves disease.
20
20
628

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c18TheEndocrineSystem.

indd Page 622 10/18/16 8:40 PM f-512 /208/WB01989/9781119287759/ch18/text_s

The Endocrine System

The Endocrine System and Homeostasis

18.2 Endocrine Glands 623

glands and hormone-producing tissues and examine how their hor-

by the Nervous and

Endocrine Systems Checkpoint

• Compare control of body functions by the nervous system and

The nervous and endocrine systems act together to coordinate functions

TA B LE 1 8 . 1 Comparison of Control by the Nervous and Endocrine Systems

CHARACTERISTIC NERVOUS SYSTEM ENDOCRINE SYSTEM

624 CH A PT E R 18 The Endocrine System

treatment of disorders of the endocrine system is known as endocri-

18.3 Hormone Activity 625

Clinical Connection Paracrine receptor

Blocking Hormone Receptors

626 CH A PT E R 18 The Endocrine System

18.4 Mechanisms of Hormone Action 627

TA B LE 1 8 . 2 Summary of Hormones by Chemical Class

CHEMICAL CLASS HORMONES SITE OF SECRETION

O CH2OH Calcitriol (active form of vitamin D). Kidneys.

Gas Nitric oxide (NO). Endothelial cells lining blood vessels.

628 CH A PT E R 18 The Endocrine System

Action of Water-Soluble Hormones

18.5 Control of Hormone Secretion 629

630 CH A PT E R 18 The Endocrine System

The anterior pituitary secretes hormones that regulate a wide range

Types of Anterior Pituitary Cells and Their

18.6 Hypothalamus and Pituitary Gland 631

FIGURE 18.5 Hypothalamus and pituitary gland.

Sagittal section of pituitary gland

Primary plexus of the

Inferior hypophyseal artery

(a) Relationship of the hypothalamus to the pituitary gland

632 CH A PT E R 18 The Endocrine System

Posterior pituitary Anterior pituitary

(b) Hypothalamic control of anterior pituitary hormone secretion

18.6 Hypothalamus and Pituitary Gland 633

TA B LE 1 8 . 3 Hormones and Cells of the Anterior Pituitary

HYPOTHALAMIC RELEASING HORMONE HYPOTHALAMIC INHIBITING HORMONE

Follicle-stimulating hormone (FSH) Gonadotrophs. Gonadotropin-releasing hormone (GnRH). —

Luteinizing hormone (LH) Gonadotrophs. Gonadotropin-releasing hormone (GnRH). —

Adrenocorticotropic hormone Corticotrophs. Corticotropin-releasing hormone (CRH). —

*Thought to exist, but exact nature is uncertain.

634 CH A PT E R 18 The Endocrine System

Somatotrophs in the anterior pituitary release bursts of growth

18.6 Hypothalamus and Pituitary Gland 635

Luteinizing Hormone In females, luteinizing hormone

636 CH A PT E R 18 The Endocrine System

TA B L E 1 8 . 4 Summary of the Principal Actions of Anterior Pituitary Hormones

HORMONE TARGET TISSUES PRINCIPAL ACTIONS

Liver (and other tissues)

Thyroid-stimulating Stimulates synthesis and secretion of thyroid hormones by thyroid gland.

Adrenocorticotropic Stimulates secretion of glucocorticoids (mainly cortisol) by adrenal cortex.

18.6 Hypothalamus and Pituitary Gland 637

Posterior Pituitary Control of Posterior Pituitary Secretion Release of

Hypothalamus Cell bodies of

(a) Hypothalamic–hypophyseal tract Figure 18.8 Continues

638 CH A PT E R 18 The Endocrine System

FIGURE 18.8 Continued

18.7 Thyroid Gland 639

TA B LE 1 8 . 5 Summary of Posterior Pituitary Hormones