4.

4 Endocrine System
The endocrine system is a regulatory system of ductless glands that secrete chemical messengers called hormones
that circulate within the body via the bloodstream to affect distant organs. Ductless glands are called endocrine
glands; they secrete hormones directly into the bloodstream for distribution throughout the body. They can be
contrasted with exocrine glands, which have ducts and secrete products into these ducts for transport to body
cavities. However, several organs and tissues such as hypothalamus and thymus, are not classified as endocrine
glands, but contain celis that secrete hormones. Hence, the endocrine system includes not only all endocrine glands
but also hormone secreting cells.
Hormones arechemical messengers (or signal molecules). According to the classical definition, hormones are
endocrine signal molecules released by cells of endocrine glands into the blood and transported tó a distantly
located target organs. According to current scientific definition: Hormones are low
molecular weight, chemically
heterogeneous non-nutrient substances which produced in trace emounts and act as intercellular signal molecules.
Even though the blood distributes hormones throughout the
body, only specific target cells can respond
to each
hormone because only the target cells have receptors for binding with the particular hormone.
 Human Plhysiology 449
Hormonal Signaling involves the blosynthesis of a particular hormone in a particular tissue, storage did
eti n
ofthe hormone, transport of thehormone to the target cell(s),
membrane or intracellular recognition of the hormone by an assoia
receptor protein, relay and amplification of the received hormonal signal via a
transduction process and a cellular response. siga
Chemical classifñication of hormones
Hormones are chemically heterogeneous and derive from
diverse precursors such
as amino acids,
GO and those
phospholipids. Chemically, they can be divided into two broad classes: those that are soluble in lipids
that are soluble in water.

Lipid-soluble hormones
The lipid-soluble
hormones include steroid hormones
and thyroid hormones.
1. Steroid hormones are derived from cholesterol.
2. Thyroid hormones (T, and T,) are synthesized by attaching iodine to the amino acid tyrosine. The benzene
of tyrosine make T and T, lipid soluble.
T
Water-soluble hormonés
The water-soluble hormones include amine hormones, peptide and protein hormones. By far the most numerous
are the protein or peptide hormones, ranging in size from just three to over 200 amino acids.

Amine hormones are acids. The

1. synthesized by decarboxylation or
modification of certain amino
epinephrine, norepinephrine and dopamine-are synthesized by modifying the amino acid tyrosine. Histamine
catecholamines
is synthesized from the amino acid histidine by mast cells and platelets. Serotonin and melatonin are derived
from tryptophan.
2. Peptide hormones and protein hormones are amino acid polymers. The smaler peptide hormones consist of
chains of 3to 49 amino acids; the larger protein hormones include 50to 200 amino acids. Examples of peptide
hormones are antidiuretic hormone andoxytocin; protein hormonesinclude human growth hormoneand insulin.
Several of the protein hormones, such as thyroid-stimulating hormone, have attached carbohydrate groups
and thus are glycoprotein hormones.

Major hormones producing endocrine glands and organs

4.4.1 Hypothalamus
It is located at the base of diencephalon of the forebrain and considered as a neuroendocrine structure rather than
a true endocrine gland. Its secretion is called neurohormone. These hormones originating in the hypothalamic
neurons, pass through axons and are released from their nerve endings. These hormones reach the pituitary gland
through a portal circulatory system and regulate the functions of the anterior pituitary. The posterior pituitary is
under the direct neural regulation of the hypothalamus.
These hormones regulate the synthesis and secretion of pituitary hormones. Depending on their actions, these
hormones are called releasing hormones (which stimulate secretion of pituitary hormones) or inhibiting hormones
(which inhibit secretions of pituitary hormones). For example, a hypothalamic hormone called Gonadotropin
releasing hormone (GnRH) stimulates the pituitary to synthesize and release of gonadotropins. On the other hand,
somatostatin from the hypothalamus inhibits the release of growth hormone from the pituitary.

Thyrotropin-releasing hormone
Thyrotropin-Releasing Hormone (TRH), also called thyrotropin-releasing factor (TRF), is a peptide hormone that
stimulates the release of thyroid-stimulating hormone (TSH) and prolactin by the anterior pituitary. TRH is produced
by the hypothalamus and travels to the pituitary via the hypophyseal portal system.

vGonadotropin-releasing hormone
Gonadotropin-Releasing Hormone (GnRH) is a peptide hormone responsible for the release of follicle stimulating
hormone (FSH) and luteinizing hormone (LH) from the anterior pituitary.
 450 Human Physiology

Growth hormone-releasing hormone

srowth Hormone-Releasing Hormone (GHRH) also known as growth hormone-releasing factor (GRF or GHRF), is
a peptide hormone produced by the hypothalamus. GHRH is released from neurosecretory nerve terminals and

carried by the hypothalamo-hypophyseal portal circulation to the anterior pituitary gland where it stimulates the

synthesis and release of growth hormone (GH).

he actions of GHRH are opposed by anether hypothalamic hormone, somatostatin, also known as growth
nOrmone-inhibiting hormone (GHIH). Somatostatin is a peptide hormone. Two active fornms of somatostatin are
yntnesized. They are referred to as somatostatin-14 and somatostatin-28, reflecting number of amino acid residues
Both forms of somatostatin are generated by proteolytic cleavage of prosomatostatin, which itself is derived from

preprosomatostatin.

Signal peptide Proteolytic cleavage

cleavage sites

Preprosomatostatin
Prosomatostatin
Somatostatin-28

Somatostatin-14
The relative amount of somatostatin-14
versus somatostatin-28 secreted
depends upon the tissue. For example,
somatostatin-14 predominates in the
hypothalamus and endocrine pancreas, but somatostatin-28 is most abundant
in the intestine. Somatostatin is
classified as an inhibitory hormone, whose main actions are to:
Inhibit the release of growth hormone
(GH).
Inhibit the release of
thyroid-stimulating hormone (TSH).
Suppress the release of gastrointestinal hormones.
Suppress the release of pancreatic hormones insulin and glucagon.
Suppress the exocrine secretory action of pancreas.
Oppose the effects of GHRH.

Corticotropin-releasing hormone
Corticotropin-Releasing Hormone (CRH), originally named corticotropin-releasing factor (CRF) and also called
corticoliberin, is a polypeptide hormone and neurotransmitter. Its main function is to stimulate the secretion of
ACTH from pituitary.

Prolactin-inhibiting hormone
Prolactin-Inhibiting Hormone (PIH), which is dopamine, inhibits the release of prolactin (PRL) from the anterior
pituitary. In the brain, dopamine also functions as a neurotransmitter, activating dopamine
receptors.
Table 4.6 Hypothalamic hormones involved in the control of the anterior
pituitary
Hormone Effect on anterior pituitary
TRH (3 amino acid residues) Stimulates secretion of TSH and
prolactin
GnRH (10 amino acid residues) Stimulates secretion of FSH and LH
GHRH (44 amino acid residues) Stimulates release of growth hormone
Somatostatin Inhibits secretion of growth hormone
CRH (41 amino acid residues)
Stimulates secretion of
ACTH
IH
Inhibits prolactin secretion
-
 Human Physiology 451

4.4.2 Pituitary gland

The pituitary gland (or hypophysis) is located in the sella turcica of
hypothalamus by inrundibulum. The sphenoid bone and is attachea to e

pituitary gland consists of two major parts in human- large anterior pituitary
(or adenohypophysis) and small
posterior pituitary (or
neurohypophysis).
Anterior pituitary
Anterior pituitary
(or 8denohypophysis)
consists of two portions, pars distalis and
humans, the pars intermedia is almost pars intermedia. However,
merged with pars distalis. Anterior pituitary secretes seven
the release of these
hormones is stimulated by o hormone
releasing hormones and suppressed by inhibiting
the hypothalamus. Pars distalis secretes
growth hormone (GH), prolactin (PRL), thyroid stimulating hormone
hormonE
TSH),adrenocorticotropic hormone (ACTH), luteinizing hormone (LH) and follicle stimulating hormone (FSH). Pars
ntermedia secretes only one hormone called
melanocyte stimulating hormone (MSH).
Some hormones regulate the production and
secretion of another hormones. A hormone that has as its primaiy
unction to regulate hormone secretion by another endocrine gland is classifñed functionally as a tropic hormone.
For example, thyroid-stimulating hormone (TSH), a tropic hormone from the anterior pituitary, stimulates thyroid
normone secretion by the thyroid gland.

Growth hormone
Growth hormone (GH or somatotropin) promotes the movement of amino acids into cells and the incorporation of
these amino acids into proteins, thus promoting overall tissue and organ growth. Growth hormone exerts its cell
division stimulating (mitogenic) effect not directly on cells but rather indirectly through the mediation of a mitogen
whose synthesis and release are induced by growth hormone. This mitogen is called insulin-like growth factor I
(IGF-I). Despite its name, this messenger has its own unique effects. Under the influence of growth hormone IGF-I
is secreted by the liver, enters the blood and functions as a hormone.

Neurosecretory cells
produce ADH and oxytocin.
Neurosecretory cells produce
hypothalamic-releasing and
hypothalamic-inhibiting
hormones.

Anterior -Posterior
pituitary pituitary

Growth hormone
Gonadotropins Oxytocin
Thyroid stimulating hormone Antidiuretic hormone
Adrenocorticotropin
Prolactin

Figure 4.24 Hypothalamus and the pituitary. The hypothalamus produces two hormones, ADH and oxytocin, which are
stored and secreted by the posterior pituitary. The hypothalamus controls the secretions of the anterior pituitary, and
the anterior pituitary controls the secretions of the thyroid, adrenal cortex and gonads, which are also endocrine glands.
 452 Human Physiology

Prolactin
Prolactin (PRL) is a peptide hormone synthesized and secreted by the adenohypophysis. Prolactin has many effects,
the most important is to stimulate the mammary glands to produce mlk (lactation). Increased serum concentration of
prolactin during pregnancy causes enlargement of the mammary glands of the breasts and increases the production
of milk. However, the high levels of progesterone during pregnancy act directly on the breasts to stop its lactogenic
effect. Milk production normaily starts when the levels of progesterone fall by the end of pregnancy. Prolactin also
gives negative feedback to hypothalamus to stop the secretion of GnRH which in turn decreases the secretion of
FSH and LH from anterior pituitary. It stops ovulation during pregnancy

Adrenocorticotropic hormone
Adrenocorticotropic hormone (ACTH or corticotropin) is a polypeptide hormone synthesized in the anterior lobe
of the pituitary gland in response to the corticotropin-releasing hormone (CRH) released by the hypothalamus. It
consists of 39 amino acids. ACTH stimulates the synthesis and secretion of steroid hormones called corticosteroids
from the adrenocortical cells of adrenal cortex.

Thyroid-stimulating hormone (TSH, thyrotropin)

TSH stimulates the synthesis and secretion of thyroid hormones from the thyroid gland.

Follicle-stimulating hormone (FSH)

Follicle-stimulating hormone stimulates gamete (ova and sperm) production in both sexes. In females, it stimulates
growth and development of ovarian follicles, within which the ova or eggs, develop. It also promotes secretion of
the estrogen by the ovaries. In males, FSH targets seminiferous tubules in testes and stimulates sperm production.

Luteinizing hormone (LH)

In females, LH triggers ovulation from Graafian follicles with the release of a secondary oocyte (future ovum) by
an ovary. LH also stimulates formation of the corpus luteum (structure formed after ovulation) in the ovary and
the secretion of progesterone by the corpus luteum. In males, it is called interstitial cell stimulating hormone
(ICSH). +t stimulates cells in the testes to secrete testosterone. LH and FSH stimulate gonadal activity and hence
are called gonadotropins.
Melanocyte-stimulating hormones (a, - and y-MSH; referred to collectively as melanotropin) act on the melanocytes
(melanin containing cells) and increases pigmentation ofthe skin in amphibians. Its exact role in humans is unknown.

Posterior pituitary (neurohypophysis)

Although the posterior pituitary or neurohypophysis does not synthesize hormones, it does store and release two
hormones: oxytocin and vasopressin. These hormones are actualy synthesised by the hypothalamus and are
transported axonally to neurohypophysis.

Oxytocin
Oxytocin (or pitocin) stimulates uterine contractions at the time of child birth that are needed to move the child
out through the birth canal. The hormone stimulates the release of milk from the mammary glands by causing
surrounding cells to contract. After birth, stimulation of the breast by the infant feeding stimulates the posterior
pituitary to produce oxytocin. It is often called as birth hormone. The function of oxytocin in males and in nonpregnant

females is not clear.

Vasopressin
Vasopressin (or pitressin) increases the resorption of water by the distal convoluted tubule and collecting duct of
the nephron and thereby reduces loss of water through urine (diuresis). Hence, it is also called as antidiuretic
hormone (ADH). The urine becomes more concentrated as water is reabsorbed. In the absence of ADH, urine output
increases more than tenfold. Drinking alcohol often causes frequent urination because alcohol inhibits secretion of
ADH. ADH also causes vasoconstriction, thereby, increasing blood pressure.
 Human Physiology 453

4.4.3 Pineal gland

The pineal gland (or epiphysis) is a small endocrine gland attached to the roof of the third ventricle of the
The gland consists of masses of neuroglia and secretory cells called
roredrdi
pinealocytes. The pineal gland secretes
an amine hormone derived from serotonin that itself is derived from the amino acid tryptophan. melatonin
Melatonin 1s the
hormone of darkness. Melatonin secretion increases up to 10-fold during the darkness of night and then talis to
low levels during the light of day. Melatonin appears to contribute to the setting of the body's biological clock. As
nore melatonin is liberated during darkness than light, this hormone is thought to promote sleepiness.
is also a potent antioxidant that may provide some protection against damaging oxygen free radicals. Melatonin ielatonun
levels are higher in children and deline with age into adulthood, but there is no evidence that changes in melatonin

secretion correlate with the onset of

puberty and sexual maturation..
The pineal gland of fish and amphibians is located near the skin and functions to detect light. In birds, it is locatea
on the brain, but receives direct light stimulus through the skull. In mammals, it is located within the brain and,

therefore, cannot receive light stimulation directly. Light from the eyes stimulates the gland via the optic nerve.

44.4 Thyroid gland

Thyroid gland 1s the largest endocrine gland in the body. It is located an ether side of the trachea. It is composed
of right and lefrt lateral lobes, one on either side of the trachea, that is connected by a fibrous connective tissue,
isthmus. It produces hormones like thyroid hormones and calcitonin.

The thyroid gland consists of numerous spherical hollow sacs called thyroid folicles and parafolicular cels. Thyroid
folidles are lined with a simple cuboidal epithelium compased of folicular cells. The interior of the follicles contains
colloid, a protein-rich fluid. The follicular cells produce two hormones: thyroxine (also called tetraiodothyronine
or T, because it contains four atoms of iodine) and triiodothyronine (or T,), which contains three atonms of iodine.
T and T, together are known as thyroid hormones.
The parafolicular cells (or C-cells) lie between follicles and secrete a hormone known as calcitonin (or thyrocalcitonin).

Colloid

cartiege

gand

C-cells secrete Follicular cells of thyroid follicle

calcitonin secrete thyroid hormone

Figure 4.25 Follicular cells enclose the follicle lumen, which is frilled with protein-rich colloid. The follicular cells
synthesize the thyroid hormones. C-cells (or parafolicular cells) are located outside the follicles; they produce the
peptide hormone calcitonin.

Production and role of thyroid hormone

The follicular cells of
thyroid follicles actively accumulate iodide from the blood and secrete it into the colloid. In
the colloid, iodide is oxidized into iodine
(21 I,) and attached to a tyrosine residue of thyroglobulin protein.
=

hyroglobulin is also synthesized and secreted by follicular cells.

The attachment of one iodine to
tyrosine produces monoiodotyrosine (MIT); the attachment of two iodines
produces
diodotyrosine (DIT). Within the colloid, enzymes modify the structure of MIT and DIT and couple them together.
 454 Human Physiology
a molecuie or tetralodothyronino
are coupled together,
When two DIT molecules that are appropriately modified Upon stimulation
forms trilodothyronine (T,).
The combination MIT with one DIT
of one
o r thyroxine), is produced.
follicular cells. Hydrolys!s reactions wilthin
are taken into the
by TSH, the thyroid homones, bound to thyroglobulin,
secreted.
the follicular cels release the free T, and T, which are
blood attached to carrier
It travels in the
n e major hormone secreted by the thyroid gland
is thyroxine (or T).
also secretes a small
amount trilodothyronine
of
proteins (Pprimarily to thyroxine-binding globulin). The thyroid
99.96% of the T, in the blood
for T. Approximately
or . The carrier proteins have a higher affinity for T, than
once the free T, passes into
emain attached to camier proteins in the plasma. Free T,
and T, enter target cells.
than T, that is active within
Hence it is the T, rather
the target cell oytoplasm, it is enzymatically converted into T.

the target cells

The actions of thyroid hormones are mediated by their binding to nuclear receptors. Receptors for
thyroid hormone
transcription factors that regulate gene
expression in target cells.
are, like all the steroid hormone receptors, act as
Unike some steroid receptors (such as glucocorticoids), thyroid hormone receptors exist in the nucleus, not the

vtoplasm, and may remain bound to DNA in the absence of hormone binding.
Thyroid hormones play an important role in the regulation of the basal metabolic rate. It increases the basal
metabolic rate in most tissues (exceptions include brain, spleen and testes) by stimulating the use ofcellular oxygen.
When the basal metabolic rate increases, cellular metabolism of carbohydrates, lipids, and proteins increases. As

ells produce and use more

ATP, more heat is generated, and body temperature rises. This phenomenon is called
the calorigenic effect.
A second major effect of thyroid hormones is to stimulate synthesisof Na-K ATPase. Togetherwith human growth
hormone andinsulin, thyroid hormones accelerate body growth, particularly the growth of the nervous and skeletal
systems.
Calcitonin is a peptide hormone secreted by parafollicular cells of the thyroid gland that are distinct from the
thyroidfollicles. Thyroid cells produce calcitonin in responseto high calcium levels in the blood. It decreases plasma
caiaum concentration by decreasing mobilization of calcium from bones; therefore promotes osteoblastic activity.

4.4.5 Parathyroid gland

The parathyroid glands are four small glands present on the back side of the thyroid gland, one pair each in the
twO lobes of the thyroid gland. They secrete parathyroid hormone (PTH) or collip's hormone, which increases levels
of caicium in the blood. Its secretion is regulated by the calcium level in the blood, (not hypothalamic or pituitary

normones). Bone tissue acts as a storage reservoir for calcium and PTH stimulates the removal of calcium from
the bone to increase levels in the blood; therefore it stimulates osteoclastic activity. It increases the reabsorption
of caicium by the renal tubules of kidney so that less is lost in urine but at the same time it stimulates the loss of
phosphates in the urine. It also stimulates kidney to secrete calcitriol which, in turn, increases calcium absorption
from the digested food in the gut. PTH is thus a hypercalcemic hormone, i.e. it increases the blood calcium levels.

4.4.6 Thymus gland

The thymus is located behind the sternum between the lungs. It grows during childhood, but gradually decreases
in size after puberty. The hormones produced by the thymus-thymosin, thymic humoral factor, thymic factor
and thymopoietin-promote the maturation of T-cells (a type of white blood cell that destroys microbes and foreign
substances) and may retard the aging process. Thymus hormones caled thymosins stimulate the development and
differentiation of T-lymphocytes or T-cell. They play a role in regulating the immune system by stimulating other
kinds of immune cells as well. It is also responsible for growth during childhood.

4.4.7 Pancreas
Pancreas is a composite gland which acts as both exocrine and endocrine gland.
The exocrine cells of
pancreas
are arranged in clusters called acini. The acini produce digestive enzymes, which flow into the gastrointestinal
 Human Physiology 455
tractthrough the
pancreatic duct. Scattered
ndocrine cells known as the islets of throughout the pancreasas between the acini are clusters, or islands, of
total pancreatic mass. Each pancreatic
Langerhans
(or pancreatic islets). The islets make
the up about 10 to 470
islet includes four
Alpha A-cells constitute about 17% of
or types of hormone-secreting cels:
B-cells pancreatic islet cells and secrete
,Beta or constitute about 70% of glucagon.
pancreatic islet cells and secrete insulin.
3Delta or D-cells constitute about 7% of
hormone-lnDing nrmone secreted by the
pancreatic islet cells
and secrete somatostatin (identical to the th
hypothalamus). Somatostatin inhibits secretion insulin
grow
qlucagon and slows absorption of nutrients from the of and

gastrointestinal tract.
4 F-cells constitute the remainder of pancreatic islet cells and
secrete pancreatic polypeptide. Pancreatic polypeptiae
inhibits somatostatin secretion,
gallbladder contraction, and secretion of
digestive enzymes by the pancreds.

Alpha cel
(secretes glucagon) Exocrine pancreas
(acinar cells and
duct cells)

Beta cell
(secretes insulin)

cell
Delta cell-
(secretes pancreatic
(secretes somatostatin) polypeptide)

Figure 4.26 The pancreatic islets or islets of Langerhans.

Glucagon and insulin

Glucagon is a linear polypeptide of 29 amino acid residues. The effects of glucagon are opposite from those of
insulin. It stimulates glycogenolysis resulting in an increased level of glucose in the blood (hyperglycemia). It also
stimulates the process of gluconeogenesis.

Function

Glycogenolysis (the breakdown of glycogen into glucose): Increase

Glycogenesis (the production of glycogen from glucose): Decrease
Gluconeogenesis (synthesis of glucose from non-carbohydrate): Increase
Triacylglycerol hydrolysis : Increase
Blood glucose level Increase
Glycolysis: Decrease
Glucose releasefrom liver: Increase

Insulin is a protein made up of two polypeptide chains designated as A (21 amino acid residues) and B (30 amino
acid residues) that are joined by two pairs of disulfide bonds with an additional intramolecular disuifide bond in
the A chain. Insulin is first synthesized as preproinsulin (110 amino acid residues). Preproinsulin is a biologically
inactive precursor. During processing of preproinsulin, removal of the signal peptide from the N-terminus of
preproinsulin generates the proinsulin molecule. Further proteolytic cleavage of proinsulin removes the C-peptide
chain producing mature insulin.
 456 Human Physiology

C chain
C chain
A chain
Removal of S
A chain Removal of Acha c chain N
signal peptide

N
N
B chain B chain
Signal B chain
peptide

Preproinsulin Proinsulin Insulin

Figure 4.27 Proteolytic cleavage is the conversion of preproinsulin into insulin.

Function
Insulin lowers blood glucose level by accelerating transport of glucose into cells.

Insulin stimulates glycogenesis in both skeletal muscle and the liver

Insulin inhibits glycogenolysis.
Insulin inhibits gluuconeogenesis in the liver.
I t enhances the entry of fatty acids from the blood into adipose tissue cells and increases lipogenesis. It
inhibits lipolysis (fat breakdown).
It stimulates protein synthesis and inhibits protein degradation.

Mechanism of glucose uptake by cell in the

presence of insulin
Insulin lowers blood glucose level by
accelerating transport of glucose into cells. Glucose transport between blood
and cells is accomplished by means of a
plasma membrane bound carrier protein known as a glucose
(GLUT). Fourteen isoforms of glucose transporters have been identified, named in the transporter
order they were discovered -

GLUT-1, GLUT-2, and so on. GLUT-4 is the only type of

transporter that responds to insulin. Unlike the other
of GLUT molecules, which are types
always present in the plasma membranes, GLUT-4 is not
membrane in the absence of insulin. It is stored in present in the plasma

the plasma
intracellular vesicles, which upon insulin stimulation, fuses with
membrane, thereby increasing the rate of sugar uptake by several-fold.
In the absence of insulin
In the presence of insulin

Glucpse Insülin binds

toreceptor

Insulinreceptor

Sna
SEa
 Human Physiology 457

Regulation of glucagon and insulin secretion

The principal action of glucagon is to increase blood
glucose level when it falls below normal. Insulin, on the
hand, helps lower bio0dglucose level when it is too o
and insutin via negative feedback.
high. The level of blood glucose controls secretion of glucagon

Low blood
glucose (hypoglycemia) High blood glucose (hyperglycemia)
stimulates alpha cells to secrete stimulates beta cells to secrete

Glucagon Insulin

Glucagon acts on hepatocytes to induce Insulin acts on various body cells to:
glycogenolysis and gluconeogenesis. Accelerate diffusion of glucose into cells.
Increase glycogenesis and lipogenesis.
Slow glycogenolysis and gluconeogenesis.
Glucose released by
hepatocytes raises
blood glucose level to normal.
Blood glucose level falls.

If bloodglucose continues to rise,

hyperglycemia inhibits release of glucagon. If blood glucose continues to fall,
hypoglycemia inhibits release of insulin.

44.8 Adrenal glands

Our body has one pair of adrenal glands, one at each kidney and is located superior to the kidney (called suprarenal
glands). They are divided into two regions - a large, peripherally located adrenal cortex, comprising 80-90% of
the gland, and a small, centrally located adrenal medulla.

Adrenal
gland- Zona
glomerulosa

Zona
fasciculata

Zona
reticularis

Left kidney

Right kidney

Figure 4.28 The location of the adrenal glands on top of the kidneys.

Adrenal cortex
he adrenal cortex is subdivided into three regions, each of which secretes different hormones. These are zona glomerulosa
une outermost layer; zona fasciculata, the middle and largest portion; and zona reticularis, the innermost zone.
 458 Human Physiology
(from zona alom

androgensglo(
merul
tos)
mineralocorticoids

hormones:
sterold
three kinds of adrenal androgens
The edrenal cortex produces hormones called (from zona
amounts of sex
and small
glucocorticoids (from zona fasoculata), as corticolds.
are commonly called
by the adrenal cortex
rebcularis). Mormones secreted mineral tons, namely sodit
homeostasis of two
Aldosterone is the major
It regulates
mineralocorticold.

body fluid volume,

osmotic pressure and
d blood eions
maintenance of electrolytes,
pressure.
and and helps in the
The renin-angBotensin-aldosterone
potassium lons, system controls secretion of aldosterone. It acts primarily ono the
on the
Increased sodium level contributes to .
excretion of potassium.
kidney to promote absorption of sodium and sOdum is excreted and
d
etention of water and thus increased blood volume.
In the absence of aldosterone, the
and lower blood pressure.
ower sodium levels result in decreased blood volume
Glucocorticolds include cortisol (hydrocortisone
Gucocorticoids carbohydrate metabolism.
are involved in
corticosterone and cortisone. The principal glucocorticoid is cortisol. The secretion of glucocorticoids is stimulated
by ACTH from the antenior pituitary. ACTH promotes the secretion of cortisol, not aldosterone. Thus, unlike cotisol
control.
egulation, the regulation of aldosterone secretion is independent of anterior pituitary

Effects of glucocorticoids
t increases the rate of protein breakdown, mainly in muscle fibers and thus increase the liberation of amino
acids into the bloodstream. It also inhibits cellular uptake and utilisation of amino acids.

It induces gluconeogenesis in liver.

It stimulates lipolysis, the breakdown of triglycerides and release of fatty acids from adipose tissue into the

blood.
It works in many ways to provide resistance to stresses, including exercise, fasting, fright, bleeding, infection
and disease.
It inhibits white blood ells that participate in inflammatory responses. Unfortunately, glucocorticoids also retard
tissue repair, and as a result, they slow wound healing.
6. High doses of glucocorticoids depress immune responses (used as immunosuppressive agent). For this reason,
glucocorticoids are prescribed for organ transplant recipients to retard tissue rejection by the immune system.

The principal adrenal androgen is DHEA (dehydroepiandrosterone). It belongs to the class of hormones known
as androgens, which also includes the major male sex hormone, testosterone, produced by the testes. It plays
more important role in female in which it promotes libido (sex drive) and is converted into estrogen by other body
tissue. After menopause, when ovarian secretion ofestrogens ceases, allfemale estrogens come from conversion of
adrenal androgens. Adrenal androgens also stimulate growth of axial hair, facial hair and pubic hair in boys and girls.

Adrenal medulla
The adrenal medulla is actualy a modified part of the sympathetic nervous system. It consists of modified
postganglionic sympathetic neurons. Unlike ordinary postganglionic sympathetic neurons, those in the adrenal
medulla do not have axons. Modified postganglionic sympathetic neurons of adrenal medula release hormones
directiy into the blood rather than releasing a neurotransmitter, the cells of the adrenal medulla secrete hormones.
The hormone-producing cells are called chromafin cells. The two major hormones synthesized by the adrenal
medulla are epinephrine (or adrenaline) and norepinephrine (or noradrenaline). The chromaffin cells of the adrenal
medulla secrete an unequal amount of these hormones-about 80% epinephrine and 20% norepinephrine. Both
epinephrine and norepinephrine are synthesized from the amino acid tyrosine. Epinephrine and norepinephrine are
collectively known as catecholamines.
In emergency or stress condition (like injury, pain, fear, accident and grief), Impulses from the hypothalamus
stimulate sympathetic preganglionic neurons, which in turn stimulate the chromaffin cells to secrete epinephrine
and norepinephrine. During emergency or stress condition, these two hormones greatly augment the fright, fight
and flight response. Hence these are called emergency hormone or hormones of Fight or Flight.
 Human Physiology 459

By increasing neart rate and force of

contraction, epinephrine and norepinephrine increase the output
o
heart,
which increases systolic blood pressure. They also
increase blood flow to the liver,acids. es, and
adipose tisSue; dilate airways to the lungs; and increase blood levels of glucoseheart,
skeietal
and fatty is
Table 4.7 Biochemical and
physiological actions of
Biochemical actions
epinephrine
CAMP level in muscle: Increase

Triacylglycerol mobilization: Increase

Glycogenolysis: Increase
Glycogen synthesis: Decrease
Physiological actions

Glucose release from liver: Increase

Glucose use by muscle: Decrease

Blood glucose level: Increase

4.4.9 Gonadal hormone

The primary reproductive organs are known as the gonads: the testes in the male and the ovaries in the female.
Gonads are the organs that produce gametes-sperm in males and oocytes in females. In addition to their reproductive
function, the gonads secrete hormones.

Endocrine part of the testes is formed by a group of cells called interstitial cells or Leydig cells. These cells secrete
male sex hormone androgen. The principal androgen is testosterone. It stimulates spermatogenesis (formation
of spermatozoa) and is responsible for the growth and development of male accessory
sex organs (like epididymis,
vas deferens, seminal vesicles, prostate gland, urethra etc.). It stimulates muscular growth, growth of facial
and axillary hair. It causes the aggressiveness, low pitch of voice and also influences the male sexual behaviour
(libido). It has a general protein anabolic (synthesis) effect and promotes bone growth, thus contributing to the
more muscular physique of males.
All androgens have actions similar to those of testosterone. Because the adrenal
androgens are much less potent
than testosterone, they are of little physiological significance in the adult male; they do, however, play roles in the
adult female, The testes also produce inhibin, which inhibits secretion of FSH.
Like testes, the ovaries also
perform endocrine function. It secretes different types of female hormones- estrogens
(estradiol and estrone), progesterone, inhibin and relaxin. Estrogen, group of steroid hormone is mainly secreted
by Graafian follicles (a mature follicle). Its secretion is stimulated by LH and FSH of the pituitary gland. The principal
estrogen is estradiol. Progesterone is secreted by the corpus luteum. The small amount of progesterone is also
secreted by the adrenal cortex and placenta. It is responsible for the maintenance of pregnancy, hence called as a
pregnancy hormone. These female sex hormones, along with FSH and LH from the anterior pituitary, regulate the

cycle, maintain pregnancy, and prepare the mammary glands for lactation. They also promote enlargement
menstrual
ofthe breasts and help maintain these female secondary sex characteristics. The ovaries also produce inhibin,a
protein hormone that inhibits secretion of follicle-stimulating hormone (FSH). During pregnancy, the ovaries and
placenta produce a peptide hormone called relaxin, which increases the flexibility of the pubic
symphysis during
pregnancy.

4.4.10 Hormones from kidney, heart, placenta and gastrointestinal tract

Cells in organs other than those usually classified as endocrine glands have an endocrine function and secrete
hormones. Organs like kidney, heart, placenta and gastrointestinal tract contain endocrine cells which secrete
hormones.
 460 Humah Physiology

Kidney into the blood

when blood volume falls a r
Ihe juxtaglomerular cells of kidney secretes an
enzyme, renin,
system. Renin catalyzes the
blood flou
ooy
to the kidneys decreases. Renin initiates the
renin-angiotensin-aldosterone

I. Angiotensin I
Is in turn hydrolyzed by
convers
anoias
of angiotensinogen, released by the liver, to anglotensin
II raises blood pressure
in two ways. First, anginto
converting enzyme to form angiotensin II. Anglotensin nsi
s a potent vasoconstrictor. Second, it stimulates secretion
of aldosterone, which
increases
tion of ssodium
reabsorption of
and water by the kidneys. The water reabsorption increases total blood volume, which increases blood prece.
ssure,
The kidneys also produce a glycoprotein hormone, erythropoietin. It stimulates the production of red blood e
d cells
in bone marow (erythropoiesis). The secretion of erythropoietin and thus the production of red blood cell
lls is
stimulated when the amount of oxygen delivered to the kidneys is lower than normal.

Placenta
Placenta secretes a variety of protein and steroid hormones. The chorionic villi of placenta secrete steroid hormones
(estrediol and progesterone) and protein hormones (human chorionic gonadotropin, HcG and Human
somatomammotropin, HCS). HCG maintains the corpus luteum for continued secretion of progesterone
Chorionie
so as
to maintain the
pregnancy. Pregnancy test is confirmed by the presence of HCG in urine. HcS stimulates the
development of the mammary glands for lactation.

Gastrointestinal tract
Endocnne cells of the
gastrointestinal tract (called enteroendocrine cells) secrete
scattered throughout the peptide hormones. These cells are
epithelium of the stomach and small intestine. Four
enteroendocrine cells major peptide hormones produce by
gastrin, secretin, cholecystokinin
are

Gastrin (G-cells of stomach

(CCK) and gastric inhibitory
peptide (GIP).
and duodenal
mucosa) acts on the gastric glands and stimulates
hydrochlonic acid and pepsinogen. It also the secretion of
increases movements of the
Secretin (S-cells of duodenal and stomach.
jejunum mucosa) increases the secretion of
pancreas and biliary tract. It
decreases gastric acid secretion and bicarbonate by the duct cells of the
pancreatic secretion of digestive aiso augments the
action of CCK in
enzymes. producing
Cholecystokinin (I-cells in the mucosa of the
system, but the most upper small intestine) performs a
important appear to number of actions in
the
the
gallbladder (the action for which it was
be the
stimulation of pancreatic
enzyme secretion, the
gastrointestinal
and pancreatic named), and relaxation of the contractionof
juice to flow into the intestinal
lumen.
sphincter of Oddi, which allows both
Gastric inhibitory bile
peptide (K-cells in the mucosa of
motility. It stimulates insulin secretion. thee duodenum and
jejunum) inhibits gastric secretion
and
Heart
The atrial wall ofour heart
secretes a very
decreases blood important peptide hormone called
pressure. When blood atrial natriuretic
vessels. This reduces the pressure is
increased, ANF is secreted which factor (ANF), which
blood pressure.
causes dilation of
Table 4.8 the blood
Major vertebrate hormones and
their chemical
nature
Gland/Hormone
Chemical class
Pituitary gland
Oxytocin
Antidiuretic hormone (ADH) Peptide
Growth hormone (GH) Peptide
Prolactin (PRL) |Protein
Protein
Follicle-stimulating hormone (FSH)D
Glycoprotein
 Human Physiology 461
Luteinizing hormone (LH)
Glycoprotein
Thyroid-stimulating hormone (TSH)
Glycoprotein
Adrenocorticotropic hormones (ACTH)
Peptide
Thyroid gland

Triodothyronine (T,) and thyroxine (T) Amine

Calaitonin
Peptide
Parathyroid glands

Parathyroid hormone (PTH)

Peptide
Pancreas

Insulin
Protein
Glucagon
Protein
Adrenal glands
Adrenal medulla

Epinephrine and norepinephrine

Amine
Adrenal cortex

Glucocorticoids, mineralocorticoids Steroid

Gonads

Testes

Androgenss Steroid
Ovaries

Estrogens Steroid
Pineal gland

Melatonin Amine

Thymus
Thymosin Peptide
Intestine
Secretin Polypeptide, 27 amino acid

Cholecystokinin Polypeptide, 23 amino acid

Gastrin Polypeptide, 17 amino acid

4.4.11 General mechanisms of hormone action

ne response to hormone both the hormone and the target cell.
a depends on

Action of lipid-soluble hormones

upid-soluble hormones, including steroid hormones and thyroid hormones, bind to receptors within
target cells. These
lipid-soluble hormones diffuse through the lipid bilayer of the plasma membrane into a cell. If the cell is
a target
cel, the hormone binds to and activates receptors located Within the cytosol or nucleus. The
intracellular receptors
dre all
related and belong to the nuclear receptor family. The receptors for the steroid hormones are
structurally
loca in the
0Cated
cytosol whereas the thyroid hormone receptor proteins are located in the nucleus. These nuclear
eceptors are transcription factors that regulate transcription of genes in response to lipophilic signal molecules. It
urns specific nuclear genes off.
on or
 462 Human Physiology
Eicosanoids (prostaglandins and
nd leukotrienes
receptors also.
Few lipophilic signal molecules bind to cell-surface
are lipid soluble hormones derived from arachidonic acid,
a 20 carbon tatty acid, but OSanoids
eicosanoids hine
bind with
cel
Surface receptors like water soluble hormones.

eceoyiael

ia bood

Target cell
Secondan
messenge

Cytoplasnie
responISE

Receptor in plasma membrane

Receptor within
the cell (cytosol or nucleus)
Figure 4.29 A
water-soluble hormone, such as
epinephrine, binds to a
receptor on or within the
to initiate an intracellular signaling cascade. A plasma membrane,
membrane of
lipid-soluble hormone, such as
estrogen, passes
a target cell, binds an intracellular receptor and changes through the plasma
gene expression.

Action of water-soluble hormones

Because amine, peptide and
protein hormones are not lipid-soluble, they cannot
the diffuse through the
plasma membrane and bind to receptors inside target cells. lipid bilayer of
that present on the target cell surface
Instead, water-soluble hormones bind to
(cell-surface receptors). The receptors are integral receptors
in the plasma membrane. When a water
soluble hormone binds to its transmembrane proteins
receptor at the outer surface of the
membrane, it acts as the first messenger. The first plasma
messenger (the hormone) then causes
messenger (including cCAMP, cGMP, diacylglycerol, inositol production of a second
cell, where specific hormone-stimulated responses take
trisphosphate, phosphoinositides and calcium) inside the
place.

4.4.12 Hormones and diseases

Hormonal disorders are
generally caused by either inadequate release
(hypersecretion) of a hormone. Other reasons for
hormonal disorders
(hyposecretion) or excessive release
inadequate number of hormone include defective hormone
receptors or defects in second messenger receptors, an
system.
 Human Physiology 463

Pituitary gland disorders

Disorders related to growth hormone

Diseases related to both hyposecretion and hypersecretion of growth hormone can occur and the symptorn per nd

on the age or the individual. Hyposecretion of growth hormone secretion during childhood causes pituitary dwarns
The predominant feature is short stature caused by retarded skeletal growth.
Hypersecretton or growth hormone during childhood causes gigantism, an abnormal increase in the length o On
hormone
of growth
bones. 1he person grows to be very tall, but body proportions are about normal. Hypersecretion
in an aduit causes acromegaly, in which the person's appearance gradually changes as a result of thickening o

bones and the growth of soft tissues, particularly in the face, hands and feet.

Disorders related to antidiuretic hormone

The abnormality associated with antidiuretic hormone is diabetes insipidus. This disorder is due to u e i

of A D .
ADH receptors inability to secrete ADH. Neurogenic diabetes insipidus results from hyposecretion
or an
nonfunctional, or
may be
nephrogenic diabetes insipidus, the kidneys do not respond to ADH. The ADH receptors
volumes
is excretion of large
the kidneys may be damaged. A common symptom of both forms of diabetes insipidus
of urine, with resulting dehydration and thirst.

Pancreatic islet disorders

is
disease in which glucOse
pancreatic disorder is diabetes mellitus. Diabetes mellitus is
a
The most common
starve
metabolized. This results in levels in blood and glucose in the urine. Cells can
not sufficiently high glucose
this disease- Type I and Type II diabetes
because glucose is not being metabolized. There are two major forms of
diabetes because the symptoms
mellitus. Type I diabetes is also called juvenile-onset diabetes or insulin-dependent
the
are necessary to treat it. It is caused by destruction of
usually appear during childhood and insulin injections
Because the disease is caused by a lack
of insulin, it can be
beta cells and the resulting lack of insulin secretion.
treated with insulin injections.
tissue sensitivity
insulin-independent diabetes (the more common form), is caused by decreased
Type iI diabetes, or
effect.
larger than normal amounts of insulin are required to produce a normal
to the effects of insulin so that

Thyroid gland disorders

the most common endocrine disorders. They fall into two major
Thyroid hormone related disorders are among
thyroid
and hormone secretion,
hyperthyroidism-reflecting deficient
excess
categories-hypothyroidism and
are largely caused by a reduction in overall metabolic activity.
respectively. The symptoms of hypothyroidism
BMR (less energy expenditure at rest); displays
with hypothyroidism has a reduced
Among other things, a patient
a tendency to gain excessive weight (not burning fuels
of the calorigenic effect); has
poor tolerance of cold (lack
has a slow, weak pulse (caused by a reduction
energy production);
at a normal rate); is easily fatigued (lower
and exhibits slow reflexes and slow
contraction and a lowered cardiac output)
in the rate and strength of cardiac

mental responsiveness.
a hallmark of this disorder is edema (accumulation of interstitial
result in myxedema,
Hypothyroidism in adults can

swell and look puffy. If a person has hypothyroidism from birth, a condition
fluid) that causes the facial tissues to
hormone are essential for normal growth and
cretinism develops. Because
adequate levels or tnyroid
known as

CNS development, cretinism is characterized

by dwarfism and mental retardation, as well as general symptoms
dwarfism, who have inadequate secretion of growth hormone from the
of thyroid deficiency. Unlike people with
mental retardation.
with cretinism suffer
severe
anterior pituitary, people
Graves disease. Ihis is an autoimmune disease in which the body
The most common cause of hyperthyroidism is an antibody whose target is the TSH receptors
immunogiobulin (Sl),
erroneously produces thyroid-stimulating
both secretion and growth of the thyroid in a manner similar to TSH. Unlike
on the thyroid cells. TSI stimulates
secretion and
negative-feedback inhibition by thyroid hormone, so thyroid
TSH, however, TSI is not subject to but not of the other types of hyperthyroidism
feature of Graves disease
growth continue unchecked. A prominent
is exophthalmos (bulging eyes).
 464 Human Physiology

Goiter
A goiter is an enlarged thyroid gland. It develops when the thyroid gland is overstimulated. A goiter
whenever either TSH or TSI excessively stimulates the thyroid gland. It may be associated with hyperthyroidic
OcCurs
hypothyroidism or euthyroidism (means normal secretion of thyroid).
roidism,
Parathyroid gland disorders
Hypoparathyroidism leads to low concentration in blood calcium levels (hypocalcemia) causing neurons and muscla
fibers to depolarize and produce action potentials spontaneously. This leads to twitches, spasms and tetany of
skeletal muscles. It is called as parathyroid tetany.
Hyperparathyroidism, an elevation in the level of parathyroid hormone, is often caused due to tumor in one of the
parathyroid gland. This causes excessive resorption of bone matrix, raising the levels of calcium and phosphate
ions in blood causing bones to become soft and easily fractured. High blood calcium levels (hypercalcemia) also
promote the formation of kidney stones.

Adrenal gland disorders

Hypersecretion of cortisol causes Cushing's syndrome. The prominent characteristics of this syndrome are related
to the exaggerated effects of glucocorticoid, with the main symptorms caused by excessive gluconeogenesis. When
too many anmino acids are converted into glucose, the body suffers from combined hyperglycemia (high blood
glucose) and protein shortage.
Addison's disease is caused by hyposecretion of both glucocorticoids and mineralocorticoids, which results in
hypoglycemia, sodium and potassium imbalance, dehydration, hypotension, rapid weight loss and generalized
weakness.

Table 4.9 A partial listing of the endocrine glands

Endccrine gland Major hormones Primary target organs
Adrenal cortex Glucocorticoids Liver and muscles

Aldosterone Kidneys
Adrenal medulla Epinephrine Heart, bronchioles and blood vessels
Hypothalamus Releasing and inhibiting hormones Anterior pituitary
Smail intestine Secretin and cholecystokinin Stomach, liver and pancreas
Islets of Langerhans Insulin Many organs
Glucagon Liver and adipose tissue

Kidneys Erythropoietin Bone marrow

Liver Somatomedins Cartilage
Ovaries Estradiol and progesterone Female reproductive tract and mammary glands
Parathyroid glands Parathyroid hormone Bone, small intestine and kidneys
Pineal gland Melatonin Hypothalamus and anterior pituitary
Pituitary, anterior Trophic hormones Endocrine glands and other organs
Pituitary, posterior Antidiuretic hormone Kidneys and blood vessels
Oxytocin Uterus and mammary glands
Stomach Gastrin
Stomach
Testes Testosterone Prostate, seminal vesicles and other organs
Thymus Thymopoietin Lymph nodes
Thyroid gland T and T, Calcitonin
Most organs