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The Endocrine System

Part A
16
Objectives
 List the major endocrine organs, and describe
their body locations.
 Distinguish between hormones, paracrines, and
autocrines.
 Chemical Classification
 Mechanisms of hormone action
 Interaction of different hormones acting on the
same target cell.
 Explain how hormone release is regulated.
 Major Endocrine Organs
 Hypothalamus and the pituitary gland.
 Adenohypophyseal hormones.
 Neurohypophysis, and its hormones
Objectives
 Thyroid gland
 Parathyroid hormone
 Adrenal gland, its hormones and their
physiological effects.
 Pancreatic hormones
 Hormones of the testes and ovaries.
 Briefly describe the importance of thymic and
pineal hormones.
 Other Hormone-Producing Structures
 Hormone produced by the heart, and localize
enteroendocrine cells.
 Hormonal functions of the placenta, kidney,
skin, and adipose tissue.
Endocrine System: Overview
 Gland--?
 Endocrine or ductless glands (endo-within; crine-
to secrete)
 Discharge hormones into the bloodstream
directly rather than through ducts e.g.,
pituitary, thyroid, adrenal.
 Exocrine glands
 Discharge their products (which are not
hormones) through ducts e.g., salivary, sweat.
 Endocrine system – Group of ductless glands
that secrete hormones necessary for normal
growth and development, reproduction, and
homeostasis. (Endocrinology)
 It is the body’s second great controlling system
which influences metabolic activities of cells by
means of hormones
 Endocrine System:
Endocrine glands – Overview
 Pituitary
 Thyroid
 Parathyroid
 Adrenal
 Pineal and Thymus
 The pancreas and gonads produce both hormones
and exocrine products
 The hypothalamus has both neural functions and
releases hormones (Neuro-endocrine Organ)
 Other tissues and organs that produce hormones –
 Adipose cells release Leptin (regulate fat storage
in the body)
 Pockets of Hormone producing cells are found in
the
 walls of the small intestine, Stomach, Kidneys,
Major Endocrine Organs and their
Location
Autocrines and Paracrines (local chemical
messengers)
 Autocrines – chemicals that exert their effects
on the same cells that secrete them
 For example, certain prostaglandins released
by smooth muscle cells cause those smooth
muscle cells to contract.
 Paracrines – locally acting chemicals that affect
cells other than those that secrete them
 e.g., somatostatin released by one population of
pancreatic cells inhibits the release of insulin
by a different population of pancreatic cells.
 These are not considered hormones since
hormones are long-distance chemical signals
 Hormones
Hormones (hormon-to excite) – chemical
substances secreted by cells into the extracellular
fluids
 Regulate the metabolic function of other cells
 Have lag times ranging from seconds to hours
 Tend to have prolonged effects
 Are classified as amino acid-based hormones, or
steroids
 The major processes controlled and integrated by
these are
1. reproduction; growth and development;
2. mobilization of body defenses;
3. maintenance of electrolyte, water, and nutrient
balance of the blood; and
4. regulation of cellular metabolism and energy
 Types
Amino ofacidHormones
based – most hormones belong to this class,
including:
 Simple AA derivatives eg Amines, thyroxine from
tyrosine
 Peptides (short chains of AA) (< 100 AA)
 Protein (Long polymers of AA) (100-200 AA)
 Steroids – (from cholesterol)
 Gonadal and adrenocortical hormones
 Eicosanoids – leukotrienes and prostaglandins
 These biologically active lipids (made from arachidonic
acid) are released by nearly all cell membranes.
 Leukotrienes  mediate inflammation and some allergic
reactions.
 Prostaglandins have multiple targets and effects,
 regulating blood pressure and increasing the expulsive
uterine contractions of birth
 Enhancing blood clotting, pain, and inflammation.
 Highly localized effects, affecting only nearby cells, they
InterActive Physiology : Endocrine System: Orientation
®

generally act as paracrines and autocrines not fit in PLAY


Types of Hormones
1. Tyrosine derivatives include
1. Hydrophilic catecholamines
 dopamine, epinephrine and
norepinephrine
2. Lipophilic thyroid hormones (T3, T4).
 Peptide hormones and glycoprotein hormones
are hydrophilic hormones stored in secretory
granules and released by exocytosis as
required.
 Steroid hormones and calcitriol are chemically
related lipophilic hormones metabolized from
cholesterol They are not stored, but are
synthesized as needed.
Hormone Action
 Hormones act only on Target cells
 Precise Response depends on target cell types
 eg Epineprine
 Vasoconstriction of smooth muscle of Blood
vessels
 Bronchodilation
 Hormones produce one or more of the following
cellular changes in target cells
 Alters plasma membrane permeability or
membrane potential, or both, by opening or
closing ion channels
 Stimulates synthesis of proteins or regulatory
molecules such as enzymes within the cell
 Activates or deactivates enzymes
 Induces secretory activity
Mechanism of Hormone
 The mechanism depends on
Action
 Chemical nature of the hormone
 Cellular location of the receptor
 Hormones alter target cell activity by one of two
mechanisms
 Second messengers involving regulatory G proteins
(Guanine Neuclotide - binding proteins)
 Direct gene activation
 Water-soluble hormones (all amino acid–based hormones except thyroid
hormone)
 Act on receptors in the plasma membrane coupled via
regulatory molecules (G proteins) to one or more
intracellular second messengers which mediate the
target cell’s response.
 Lipid-soluble hormones (steroid and thyroid hormones)
 Act on intracellular receptors, directly activating genes.
 The precise response depends on the type of the target
Hydrophilic hormones : (G-protein Coupled 2nd messengers)
Lipid-soluble hormones: (Intracellular Receptors
Mediated)
Amino Acid-Based Hormone Action: cAMP
Second Messenger

 Hormone (first messenger) binds to its receptor,


which then binds to a G protein
 The G protein is then activated as it binds GTP,
displacing GDP
 Activated G protein activates the effector
enzyme adenylate cyclase
 Adenylate cyclase generates cAMP (second
messenger) from ATP
 cAMP activates protein kinases, which then
cause cellular effects
Amino Acid-Based Hormone Action: cAMP
Second Messenger
Amino Acid-Based Hormone Action:
PIP-Calcium

 Hormone binds to the receptor and activates


G protein
 G protein binds and activates a phospholipase
enzyme
 Phospholipase splits the phospholipid PIP2 into
diacylglycerol (DAG) and IP3 (both act as
second messengers)
 DAG activates protein kinases; IP3 triggers
release of Ca2+ stores
 Ca2+ (third messenger) alters cellular responses
Amino Acid-Based Hormone Action:
PIP-Calcium
cAMP Second Messenger & Ca++
Pathways
Steroid Hormones

 Steroid hormones and thyroid hormone diffuse easily


into their target cells
 Once inside, they bind and activate a specific
intracellular receptor
 The hormone-receptor complex travels to the nucleus
and binds a DNA-associated receptor protein
 This interaction prompts DNA transcription to
produce mRNA
 The mRNA is translated into proteins, which bring
about a cellular effect
Steroid Hormones
Steroid Hormones: (Aldosteron)
Target Cell Specificity

 Hormones circulate to all tissues but only


activate cells referred to as target cells
 Target cells must have specific receptors to
which the hormone binds
 These receptors may be intracellular or located
on the plasma membrane
 Examples of hormone activity
 ACTH receptors are only found on certain
cells of the adrenal cortex
 Thyroxin receptors are found on nearly all
cells of the body
Target Cell Activation
 Target cell activation depends on three factors
 Blood levels of the hormone
 Relative number of receptors on the target cell
 The affinity of those receptors for the hormone
 Up-regulation – target cells form more receptors in
response to the hormone
 Down-regulation – target cells lose receptors in
response to the hormone
 Hormones influence the number and affinity not
only of their own receptors but also of receptors
that respond to other hormones.
 For example, progesterone induces a loss of
estrogen receptors in the uterus, On the other
hand, estrogen causes the same cells to produce
more progesterone receptors, enhancing their
ability to respond to progesterone.
PLAY InterActive Physiology®: Endocrine System: Actions of Hormones on Target Cells
Hormone Concentrations in the Blood
 Hormones circulate in the blood in two forms –
free or bound
 Steroids and thyroid hormone are attached to
plasma proteins
 All others are free to move
 Concentrations of circulating hormone reflect:
 Rate of release
 Speed of inactivation and
 removal from the body
 Hormones are removed from the blood by:
 Degrading enzymes
 The kidneys
 Liver enzyme systems
Interaction of Hormones at Target Cells
 Three types of hormone interaction
 Permissiveness – one hormone cannot exert its effects
without another hormone being present
 For example, the development of the reproductive
system by its hormones but thyroid hormone is
necessary for normal timely development of
reproductive structures
 Synergism – more than one hormone produces the same
effects on a target cell
 For example, both glucagon (produced by the
pancreas) and epinephrine cause the liver to release
glucose to the blood; when they act together, the
amount of glucose released is about 150% of what is
released when each hormone acts alone.
 Antagonism – one or more hormones opposes the action
of another hormone
 Insuline vs glucagon
Hormone Action, Release and Control

 The duration of hormone action is limited,


ranging from 10 seconds to several hours,
depending on the hormone.
 Hormonal blood levels must be precisely and
individually controlled to meet the continuously
changing needs of the body.
 Blood levels of hormones:
 Are controlled by negative feedback systems
 Vary only within a narrow desirable range
InterActive Physiology®:
PLAY
Endocrine System: Biochemistry, Secretion, and Transport of Hormones
Feed Back Mechanisms
Feed Back Mechanisms
Control of Hormone Release

 Hormones are synthesized and released in


response to following stimuli
 Humoral
 Neural
 Hormonal
Humoral Stimuli

 Humoral stimuli – secretion of hormones in


direct response to changing blood levels of ions
and nutrients
 Example: concentration of calcium ions in the
blood
 Declining blood Ca2+ concentration stimulates
the parathyroid glands to secrete PTH
(parathyroid hormone)
 PTH causes Ca2+ concentrations to rise and the
stimulus is removed
Humoral Stimuli
Neural Stimuli

 Neural stimuli – nerve


fibers stimulate
hormone release
 Preganglionic
sympathetic nervous
system (SNS) fibers
stimulate the adrenal
medulla to secrete
catecholamines
Hormonal Stimuli

 Hormonal stimuli – release of hormones in


response to hormones produced by other
endocrine organs
 The hypothalamic hormones stimulate the
anterior pituitary
 In turn, pituitary hormones stimulate targets
to secrete still more hormones
 eg, Thyroid, Adrenal, Gonads etc.
Hormonal Stimuli
Nervous System Modulation

 The nervous system modifies the stimulation of


endocrine glands and their negative feedback
mechanisms
 The nervous system can override normal
endocrine controls
 For example, control of blood glucose levels
 Normally the endocrine system maintains
blood glucose (90-110mg/100ml of blood)
 Under stress, the body needs more glucose
 The hypothalamus and the sympathetic
nervous system are activated to supply
ample glucose
Functional classification of hormones
 Hormones are classified into two functional categories:
1. Trophic hormones
2. Nontrophic hormones
 Trophic hormone
 Acts on another endocrine gland to stimulate secretion of
its hormone.
 For example, Thyrotropin or TSH stimulates the secretion
of thyroid hormones.
 ACTH stimulates the adrenal cortex to secrete the
hormone cortisol.
 Nontrophic hormone
 Acts on nonendocrine target tissues.
 For example, Parathormone bone tissue to stimulate the
release of calcium into the blood.
 Aldosterone acts on the kidney to stimulate the
reabsorption of sodium into the blood.
Major Endocrine Organs

1. Pituitary (Hypophysis)
2. Thyroid
3. Parathyroid
4. Adrenal or Supra-Renal
5. Pancreas
6. Gonads
7. Pineal
8. Thymus
Major Endocrine Organs: Pituitary
(Hypophysis)
 Pituitary gland – two-lobed organ that secretes nine major
hormones
 About the size and shape of a Pea or Almond
 Lies in the sella turcica, a bony cavity at the base of the
brain
 In humans, the pituitary gland has two major lobes
 Posterior Pituitary Lobe
 Anterior Pituitary Lobe
 Posterior lobe – Neurohypophysis (neural tissue) and the
infundibulum (funnel shaped connecting stalk)
 Receives, stores, and releases hormones from the
hypothalamus
 Anterior lobe – Adenohypophysis made up of glandular
tissue
 Synthesizes and secretes a number of hormones
Major Endocrine Organs: Pituitary
(Hypophysis)
Pituitary-Hypothalamic Relationships:
Posterior Lobe
 The posterior lobe is a down growth of
hypothalamic neural tissue
 Connected to hypothalamus through nerve bundle
callled (hypothalamic-hypophyseal tract)
 This tract arises from neurons in the supraoptic and
paraventricular nuclei of the hypothalamus
 Nuclei of the hypothalamus synthesize two
hormones
 ADH (supraoptic)
 Oxytocin (paraventricular)
 These hormones are transported to the posterior
pituitary
 Stored hormones are released in general
circulation when hypothalamic neurons fire.
Pituitary-Hypothalamic Relationships:
Anterior Lobe

  The glandular anterior lobe originates from a


superior out pocketing of the oral mucosa and is
formed from epithelial tissue
 There is no direct neural contact with the
hypothalamus but there is a vascular connection
 This vascular connection, the hypophyseal portal
system, consists of:
 The primary capillary plexus (in infundibulum)
 The hypophyseal portal veins
 The secondary capillary plexus (in anterior lobe)

PLAY InterActive Physiology®: Endocrine System: The Hypothalamic-Pituitary Axis


Major Endocrine Organs: Pituitary (
Hypophysis)
Adenophypophyseal Hormones
 The six hormones of the adenohypophysis, all of them
proteins,
 Are abbreviated as GH, TSH, ACTH, FSH, LH, and PRL
 Regulate the activity of other endocrine glands
 In addition, pro-opiomelanocortin (POMC) has been
isolated from the pituitary
 POMC is a prohormone, can split enzymatically into one
or more active hormones.
 POMC is the source of
 Adrenocorticotropic hormone,
 Two natural opiates Enkephalin and Beta endorphin
 Melanocyte-stimulating hormone (MSH).
 In Animals MSH melanocytes  melanin pigment
synthesis
 In humans, MSH is a CNS neurotransmitter that controls
appetite.
Adenophypophyseal Hormones
Hypothalamu Secreting Hormone Chemical Nature
s Hormones Cells
GHIH Somatotroph Growth Hormone Protein
GHRH (30-40%) (GH) (Single chain 191 AA)
CRH Corticotroph Adrenocorticotropi Polypeptide
c Hormone (Single chain 39 AA)
(ACTH)
TRH Thyrotroph Thyroid Glycoprotein
Stimulating ( α-89 amino acids)
Hormone (TSH) (ß-112 amino acids)
Gonadotroph Follicle stimulating Glycoprotein
GnRH Hormone (FSH) ( α-89 amino acids)
(ß-112 amino acids)
GnRH Gonadotroph Luteinizing Glycoprotein
Hormone (LH) ( α-89 amino acids)
(ß-115 amino acids)
PIH Lactotroph Prolactin (PRL) Protein
(Single chain 198 AA)
Activity of the Adenophypophysis

 The hypothalamus sends a chemical stimulus


to the anterior pituitary
 Releasing hormones stimulate the synthesis and
release of hormones
 Inhibiting hormones shut off the synthesis and
release of hormones
Hypothalamic Releasing and Inhibitory Hormones That Control Secretion of the
Anterior Pituitary Gland
Hormone Chemical Nature Primary Action on
Anterior Pituitary
Thyrotropin-releasing Peptide of 3 amino acids Stimulates secretion of
hormone (TRH) TSH by thyrotropes
Gonadotropin-releasing Single chain of 10 amino Stimulates secretion of
hormone (GnRH) acids FSH and LH by
gonadotropes
Corticotropin-releasing Single chain of 41 amino Stimulates secretion of
hormone (CRH) acids ACTH by corticotropes

Growth hormone Single chain of 44 amino Stimulates secretion of


releasing hormone acids growth hormone by
(GHRH) somatotropes
Growth hormone Single chain of 14 amino Inhibits secretion of
inhibitory hormone acids growth hormone by
(GHIH) somatotropes
Prolactin-inhibiting Dopamine (a Inhibits secretion of
hormone (PIH) catecholamine) prolactin by lactotropes
Growth Hormone (GH)

 Growth hormone (GH) is produced by cells called


somatotrophs of the anterior lobe.
 It is a 191-amino acid, single-chain protein hormone
 GH stimulates most body cells to increase in size and
divide, its major targets are
 Bones & Skeletal muscles.
 Stimulation of the epiphyseal plate leads to long bone
growth
 Stimulation of skeletal muscles promotes increased muscle
mass.
 Essentially an anabolic (tissue-building) hormone that,
 Promotes protein synthesis,
 Encourages the use of fats for fuel,
 Conserves glucose
Growth Hormone (GH) Metabolic
Actions
 Indirect Actions:
 Most effects are mediated indirectly by insulin-like
growth factors (IGFs) or somatomedins.
 These are a family of growth-promoting proteins
produced by
 The liver,
 Skeletal muscle,
 Bone, and other tissues.
 IGFs Specifically,
 Stimulate uptake of amino acids from the blood for
cellular proteins synthesis
 Stimulate uptake of sulfur into cartilage matrix
 (Needed for the synthesis of chondroitin
Growth Hormone (GH) Metabolic
Actions
 Direct Actions
 GH mobilizes fats from fat depots for transport to cells,
increasing blood levels of fatty acids.
 It decreases the rate of glucose uptake and metabolism.
 In the liver, it encourages glycogen breakdown and
release of glucose to the blood.
 Diabetogenic effect of GH due to glucose sparing
 Regulation of GH release
 Antagonistic hypothalamic hormones regulate GH
 Growth hormone–releasing hormone (GHRH)
stimulates GH release
 Growth hormone–inhibiting hormone (GHIH) inhibits
GH release
Metabolic Action of Growth Hormone

Figure 16.6
Gigantism & Acromegaly
 Hypersecretion in children results in gigantism
 The person becomes abnormally tall, often reaching a
height of 2.4 m (8 feet), but has relatively normal body
proportions.
 Acromegaly literally translated as “enlarged extremities,”
 If excessive amounts of GH are secreted after the
epiphyseal plates have closed,
 This condition is characterized by overgrowth of bony
areas still responsive to GH, namely bones of the hands,
feet, and face.
 Hypersecretion usually results from an
adenohypophyseal tumor that releases excessive amounts
of GH
 Usual treatment is surgical removal of the tumor
 Anatomical changes that have already occurred are not
reversible.
Dwarfism
 Hyposecretion of GH in adults usually causes no
problems.
 GH deficiency in children results in slowed long bone
growth, a condition called pituitary dwarfism.
 Such individuals attain a maximum height of 1.2 m (4
feet), but usually have fairly normal body proportions.
 Lack of GH is often accompanied by deficiencies of
other adenohypophyseal hormones, and if thyroid-
stimulating hormone and gonadotropins are lacking,
the individual will be malproportioned and will fail to
mature sexually as well.
 Treatment
 When pituitary dwarfism is diagnosed before puberty,
growth hormone replacement therapy can promote
nearly normal somatic growth.
Gigantism & Acromegaly
Thyroid Stimulating Hormone
(Thyrotropin)

 Tropic hormone that stimulates the normal


development and secretory activity of the
thyroid gland
 Triggered by hypothalamic peptide
thyrotropin-releasing hormone (TRH)
 Rising blood levels of thyroid hormones act on
the pituitary and hypothalamus to block the
release of TSH
Adrenocorticotropic Hormone
(Corticotropin)

 Stimulates the adrenal cortex to release


corticosteroids
 Triggered by hypothalamic corticotropin-
releasing hormone (CRH) in a daily rhythm
 Internal and external factors such as fever,
hypoglycemia, and stressors can trigger the
release of CRH
Gonadotropins

 Gonadotropins – follicle-stimulating hormone


(FSH) and luteinizing hormone (LH)
 Regulate the function of the ovaries and testes
 FSH stimulates gamete (egg or sperm)
production
 Absent from the blood in prepubertal boys
and girls
 Triggered by the hypothalamic gonadotropin-
releasing hormone (GnRH) during and after
puberty
Functions of Gonadotropins

 In females
 LH works with FSH to cause maturation of the
ovarian follicle
 LH works alone to trigger ovulation
(expulsion of the egg from the follicle)
 LH promotes synthesis and release of
estrogens and progesterone
Functions of Gonadotropins

 In males
 LH stimulates interstitial cells of the testes to
produce testosterone
 LH is also referred to as interstitial cell-
stimulating hormone (ICSH) in males.
Prolactin (PRL)

 In females, stimulates milk production by the


breasts
 Triggered by the hypothalamic prolactin-releasing
hormone (PRH)
 Inhibited by prolactin-inhibiting hormone (PIH)
 Blood levels rise toward the end of pregnancy
 Suckling stimulates PRH release and encourages
continued milk production
 In females, prolactin levels rise and fall in rhythm
with estrogen blood levels.
 Estrogen stimulates prolactin release, both directly
and indirectly.
The Posterior Pituitary and
Hypothalamic Hormones

 Posterior pituitary – made of axons of


hypothalamic neurons, stores antidiuretic
hormone (ADH) and oxytocin
 ADH and oxytocin are synthesized in the
hypothalamus
 ADH influences water balance
 Oxytocin stimulates smooth muscle contraction
in breasts and uterus
 Both use PIP-calcium second-messenger
mechanism
Oxytocin
 Oxytocin is a strong stimulant of uterine
contraction
 Regulated by a positive feedback mechanism to
oxytocin in the blood
 This leads to increased intensity of uterine
contractions, ending in birth
 Oxytocin triggers milk ejection (“letdown”
reflex) in women producing milk
 Synthetic and natural oxytocic drugs are used to
induce or hasten labor
 Plays a role in sexual arousal and satisfaction in
males and nonlactating females
Antidiuretic Hormone (ADH)
 ADH helps to avoid dehydration or water
overload
 Prevents urine formation
 Osmoreceptors monitor the solute concentration
of the blood
 With high solutes, ADH is synthesized and
released, thus preserving water
 With low solutes, ADH is not released, thus
causing water loss from the body
 Alcohol inhibits ADH release and causes
copious urine output