WEEK 2

CLASSIFICATION OF HORMONES
• Based on chemical nature, hormones are
classified into three types:

• 1. Steroid hormones

• 2. Protein hormones

• 3. Derivatives of the amino acid called

tyrosine.
 STEROID HORMONES
• Steroid hormones are the hormones
synthesized from cholesterol or its derivatives.
• Steroid hormones are secreted by adrenal
cortex, gonads and placenta.
• Although there is usually very little hormone
storage in steroid-producing endocrine cells,
large stores of cholesterol esters in cytoplasm
vacuoles can be rapidly mobilized for steroid
synthesis after a stimulus.
 STEROID HORMONES Contd

• Much of the cholesterol in steroid-producing

cells comes from the plasma, but there is also
de novo synthesis of cholesterol in steroid-
producing cells.

• Because the steroids are highly lipid soluble,

once they are synthesized, they simply diffuse
across the cell membrane and enter the
interstitial fluid and then the blood.
 PROTEIN HORMONES
• Protein hormones are large or small peptides.
• Protein hormones are secreted by pituitary
gland, parathyroid glands, pancreas and
placenta (‘P’s).
• Most of the hormones in the body are
polypeptides and proteins.
• These hormones range in size from small
peptides with as few as 3 amino acids
(thyrotropin-releasing hormone) to proteins
with almost 200 amino acids (growth hormone
and prolactin).
 PROTEIN HORMONES Contd
• In general, polypeptides with 100 or more amino
acids are called proteins, and those with fewer
than 100 amino acids are referred to as peptides.
• Protein and peptide hormones are synthesized on
the rough end of the endoplasmic reticulum of the
different endocrine cells, in the same fashion as
most other proteins.
• They are usually synthesized first as larger proteins
that are not biologically active (preprohormones)
and are cleaved to form smaller prohormones in
the endoplasmic reticulum.
 PROTEIN HORMONES Contd
• These are then transferred to the Golgi apparatus for
packaging into secretory vesicles.
• In this process, enzymes in the vesicles cleave the
prohormones to produce smaller, biologically active
hormones and inactive fragments.
• The vesicles are stored within the cytoplasm, and
many are bound to the cell membrane until their
secretion is needed.
• Secretion of the hormones (as well as the inactive
fragments) occurs when the secretory vesicles fuse
with the cell membrane and the granular contents are
extruded into the interstitial fluid or directly into the
blood stream by exocytosis.
 PROTEIN HORMONES Contd
• In many cases, the stimulus for exocytosis is an
increase in cytosolic calcium concentration caused
by depolarization of the plasma membrane.
• In other instances, stimulation of an endocrine cell
surface receptor causes increased cyclic
adenosine monophosphate (cAMP) and
subsequently activation of protein kinases that
initiate secretion of the hormone.
• The peptide hormones are water soluble, allowing
them to enter the circulatory system easily, where
they are carried to their target tissues.
 TYROSINE DERIVATIVES
• Two types of hormones, namely thyroid
hormones and adrenal medullary hormones are
derived from the amino acid tyrosine.
• They are formed by the actions of enzymes in
the cytoplasmic compartments of the glandular
cells.
• The thyroid hormones are synthesized and
stored in the thyroid gland and incorporated
into macromolecules of the protein
thyroglobulin, which is stored in large follicles
within the thyroid gland.
 TYROSINE DERIVATIVES Contd.
• Hormone secretion occurs when the amines are
split from thyroglobulin, and the free hormones
are then released into the blood stream.
• After entering the blood, most of the thyroid
hormones combine with plasma proteins,
especially thyroxine binding globulin, which slowly
releases the hormones to the target tissues.
• Epinephrine and norepinephrine are formed in the
adrenal medulla, which normally secretes about
four times more epinephrine than
norepinephrine.
 TYROSINE DERIVATIVES Contd.
• Catecholamines are taken up into preformed
vesicles and stored until secreted.
• Similar to the protein hormones stored in
secretory granules, catecholamines are also
released from adrenal medullary cells by
exocytosis.
• Once the catecholamines enter the
circulation, they can exist in the plasma in free
form or in conjugation with other substances.
 WEEK 3-4
The Pituitary Hormones and
Hypothalamic Control
 Pituitary gland

• Pituitary gland or hypophysis is a small

endocrine gland with a diameter of 1 cm and
weight of 0.5 to 1 g.
• It is situated in a depression called ‘sella
turcica’, present in the sphenoid bone at the
base of skull.
• It is connected with the hypothalamus by the
pituitary stalk or hypophyseal stalk.
 DIVISIONS OF PITUITARY GLAND
Pituitary gland is divided into two divisions:

• 1. Anterior pituitary or adenohypophysis

• 2. Posterior pituitary or neurohypophysis.

• Both the divisions are situated close to each other.

Still both are entirely different in their development,
structure and function.

• Between the two divisions, there is a small and

relatively avascular structure called pars intermedia.
Actually, it forms a part of anterior pituitary.
• Pituitary gland
 Hypothalamo-hypophyseal Relationship
• The relationship between hypothalamus and
pituitary gland is called hypothalamo-hypophyseal
relationship.
• Hormones secreted by hypothalamus are
transported to anterior pituitary and posterior
pituitary differently.
• Hormones from hypothalamus are transported to
anterior pituitary through hypothalamo-hypophysial
portal blood vessels.
• But, the hormones from hypothalamus to posterior
pituitary are transported by nerve fibers of
hypothalamo-hypophyseal tract.
ANTERIOR PITUITARY OR ADENOHYPOPHYSIS
• Anterior pituitary is also known as the master
gland because it regulates many other
endocrine glands through its hormones.

PARTS
• 1. Pars distalis
• 2. Pars tuberalis
• 3. Pars intermedia.
 REGULATION OF ANTERIOR PITUITARY
SECRETION
• Hypothalamus controls anterior pituitary by secreting the
releasing and inhibitory hormones (factors), which are called
neurohormones.
• These hormones from hypothalamus are transported to anterior
pituitary through hypothalamo-hypophyseal portal vessels.
• Some special nerve cells present in various parts of
hypothalamus send their nerve fibers (axons) to median
eminence and tuber cinereum.
• These nerve cells synthesize the hormones and release them
into median eminence and tuber cinereum.
• From here, the hormones are transported by blood via
hypothalamo-hypophyseal portal vessels to anterior pituitary.
 Releasing and Inhibitory Hormones
Secreted by Hypothalamus
• 1. Growth hormone-releasing hormone (GHRH): Stimulates
the release of growth hormone
• 2. Growth hormone-releasing polypeptide (GHRP): Stimulates
the release of GHRH and growth hormone
• 3. Growth hormone-inhibitory hormone (GHIH) or
somatostatin: Inhibits the growth hormone release
• 4. Thyrotropic-releasing hormone (TRH): Stimulates the
release of thyroid stimulating hormone
• 5. Corticotropin-releasing hormone (CRH): Stimulates the
release of adrenocorticotropin
• 6. Gonadotropin-releasing hormone (GnRH): Stimulates the
release of gonadotropins, FSH and LH
• 7. Prolactin-inhibitory hormone (PIH): Inhibits prolactin
secretion. It is believed that PIH is dopamine.
 HORMONES SECRETED BY ANTERIOR PITUITARY
• Six hormones are secreted by the anterior pituitary:
• 1. Growth hormone (GH) or somatotropic hormone
(STH)
• 2. Thyroid-stimulating hormone (TSH) or thyrotropic
hormone
• 3. Adrenocorticotropic hormone (ACTH)
• 4. Follicle-stimulating hormone (FSH)
• 5. Luteinizing hormone (LH) in females or interstitial
cell-stimulating hormone (ICSH) in males
• 6. Prolactin.
• Recently, the hormone ß-lipotropin is found to be
secreted by anterior pituitary.
 NOTE
• The first five hormones of anterior pituitary
stimulate the other endocrine glands and are
named tropic hormones

• FSH and LH are together called gonadotropic

hormones or gonadotropins because of their
action on gonads.
 GROWTH HORMONE
• Growth hormone is secreted by somatotropes which
are the acidophilic cells of anterior pituitary.
• GH is protein in nature, having a single-chain
polypeptide with 191 amino acids with molecular
weight of 21,500.
• Basal level of GH concentration in blood of normal
adult is up to 300 g/dL and in children, it is up to 500
ng/dL. Its daily output in adults is 0.5 to 1.0 mg.
• Growth hormone is transported in blood by GH-
binding proteins (GHBPs).
• Half-life of circulating growth hormone is about 20
minutes. It is degraded in liver and kidney.
 Actions of Growth Hormone
• GH is responsible for the general growth of the
body.
• It increases the size and number of cells by
mitotic division.
• GH also causes specific differentiation of certain
types of cells like bone cells and muscle cells.
• Hypersecretion of GH causes enormous growth
of the body, leading to gigantism.
• Deficiency of GH in children causes stunted
growth, leading to dwarfism.
 Effect of GH on protein metabolism
• GH accelerates the synthesis of proteins by:
• i. The concentration of amino acids in the cells increases
and thus, the synthesis of proteins is accelerated.
• ii. GH increases the translation of RNA in the cells.
Because of this, ribosomes are activated and more proteins
are synthesized. GH can increase the RNA translation
even without increasing the amino acid transport into the
cells.
• iii. It also stimulates the transcription of DNA to RNA.
RNA, in turn accelerates the synthesis of proteins in the
cells.
• iv. GH inhibits the breakdown of cellular
protein. It helps in the building up of tissues.

• v. GH increases the release of insulin (from ß-

cells of islets in pancreas), which has anabolic
effect on proteins.
 Effect on fat metabolism
• GH mobilizes fats from adipose tissue. So, the
concentration of fatty acids increases in the body
fluids.
• These fatty acids are used for the production of
energy by the cells. Thus, the proteins are spared.
• During the utilization of fatty acids for energy
production, lot of acetoacetic acid is produced by
liver and is released into the body fluids, leading to
ketosis.
• Sometimes, excess mobilization of fat from the
adipose tissue causes accumulation of fat in liver,
resulting in fatty liver.
 Effects of GH on carbohydrate metabolism
• i. Decrease in the peripheral utilization of glucose for
the production of energy:
• It is because of the formation of acetyl-CoA during
the metabolism of fat, influenced by GH. The acetyl-
CoA inhibits the glycolytic pathway.
• Moreover, since the GH increases the mobilization of
fat, more fatty acid is available for the production of
energy. By this way, GH reduces the peripheral
utilization of glucose for energy production.
• ii. Increase in the deposition of glycogen in the cells:
Since glucose is not utilized for energy production by
the cells, it is converted into glycogen and deposited
in the cells.
• iii. Decrease in the uptake of glucose by the cells: As
glycogen deposition increases, the cells become saturated
with glycogen.
• Because of this, no more glucose can enter the cells from
blood. So, the blood glucose level increases.
• iv. Diabetogenic effect of GH: Hypersecretion of GH
increases blood glucose level enormously. It causes
continuous stimulation of the ß-cells in the islets of
Langerhans in pancreas and increase in secretion of
insulin.
• In addition to this, the GH also stimulates ß-cells directly
and causes secretion of insulin. Because of the excess
stimulation, ß-cells are burnt out at one stage.
• This causes deficiency of insulin, leading to true diabetes
mellitus or full-blown diabetes mellitus. This effect of GH
 Effects of GH On bones
• In embryonic stage, GH is responsible for the
differentiation and development of bone cells.
• In later stages, GH increases the growth of the skeleton. It
increases both the length as well as the thickness of the
bones.
• In bones, GH increases:
• i. Synthesis and deposition of proteins by chondrocytes
and osteogenic cells
• ii. Multiplication of chondrocytes and osteogenic cells by
enhancing the intestinal calcium absorption
• iii. Formation of new bones by converting chondrocytes
into osteogenic cells
• iv. Availability of calcium for mineralization of bone matrix.
• Hypersecretion of GH before the fusion of
epiphysis with the shaft of the bones causes
enormous growth of the skeleton, leading to a
condition called gigantism.
• Hypersecretion of GH after the fusion of
epiphysis with the shaft of the bones leads to
a condition called acromegaly.
 Mode of Action of GH – Somatomedin
• GH acts on bones, growth and protein
metabolism through somatomedins secreted by
liver.
• GH stimulates the liver to secrete several small
proteins called somatomedins.
• It is a polypeptide with the molecular weight of
about 7,500.
• Many of the somatomedin effects on growth are
similar to the effects of insulin on growth.
• Therefore, the somatomedins are also called
insulin-like growth factors (IGFs).
 Types of somatomedin
• About four types of somatomedins have been
isolated. The common two types are:
• i. Insulin-like growth factor-I (IGF-I), which is also
called somatomedin C
• ii. Insulin-like growth factor-II.
• Somatomedin C (IGF-I) acts on the bones and
protein metabolism. Insulin-like growth factor-II
plays an important role in the growth of fetus.
• Sometimes, in spite of normal secretion of GH,
growth is arrested (dwarfism) due to the
absence or deficiency of somatomedin C.
• The pygmies of Africa have a congenital inability
to synthesize significant amounts of
somatomedin C.

• Therefore, even though their plasma

concentration of growth hormone is either
normal or high, they have diminished amounts of
somatomedin C in the plasma which apparently
accounts for the small stature of these people.
 Duration of action of GH and somatomedin C
• GH is transported in blood by loose binding with plasma
protein. So, at the site of action, it is released from
plasma protein rapidly.
• Its action also lasts only for a short duration of 20
minutes.
• But, the somatomedin C binds with plasma proteins very
strongly. Because of this, the molecules of somatomedin
C are released slowly from the plasma proteins.
• Thus, it can act continuously for a longer duration. The
action of somatomedin C lasts for about 20 hours.
• Mode of action of somatomedin C
• Somatomedin C acts through the second messenger
called cyclic AMP.
 Regulation of GH Secretion
• Growth hormone secretion is altered by various factors.
However, hypothalamus and feedback mechanism play an
important role in the regulation of GH secretion
• GH secretion is stimulated by:
• 1. Hypoglycemia
• 2. Fasting
• 3. Starvation
• 4. Exercise
• 5. Stress and trauma
• 6. Initial stages of sleep.
• GH secretion is inhibited by:
• 1. Hyperglycemia
• 2. Increase in free fatty acids in blood
• 3. Later stages of sleep.
 Role of hypothalamus in the secretion of GH
• Hypothalamus regulates GH secretion via three hormones:
• 1. Growth hormone-releasing hormone (GHRH): It increases
the GH secretion by stimulating the somatotropes of anterior
pituitary
• 2. Growth hormone-releasing polypeptide (GHRP): It
increases the release of GHRH from hypothalamus and GH
from pituitary
• 3. Growth hormone-inhibitory hormone (GHIH) or
somatostatin: It decreases the GH secretion. Somatostatin is
also secreted by delta cells of islets of Langerhans in
pancreas.
• These three hormones are transported from hypothalamus
to anterior pituitary by hypothalamohypophyseal portal
blood vessels.
 NEGATIVE FEEDBACK CONTROL OF GH

Key: green line = stimulation/secretion

Red dotted line= inhibition
• GH secretion is under negative feedback control.
• Hypothalamus releases GHRH and GHRP, which
in turn promote the release of GH from anterior
pituitary.
• GH acts on various tissues. It also activates the
liver cells to secrete somatomedin C (IGF-I).
• Now, the somatomedin C increases the release
of GHIH from hypothalamus. GHIH, in turn
inhibits the release of GH from pituitary.
• Somatomedin also inhibits release of GHRP from
hypothalamus. It acts on pituitary directly and
inhibits the secretion of GH .
• GH inhibits its own secretion by stimulating the
release of GHIH from hypothalamus.

• This type of feedback is called short-loop

feedback control. Similarly, GHRH inhibits its own
release by short-loop feedback control.

• Whenever, the blood level of GH decreases, the

GHRH is secreted from the hypothalamus. It in
turn causes secretion of GH from pituitary.
 OTHER ANTERIOR PITUITARY HORMONES
• Thyroid-stimulating Hormone (TSH)
• TSH is necessary for the growth and secretory
activity of the thyroid gland. It has many actions on
the thyroid gland.
• Adrenocorticotropic Hormone (ACTH)
• ACTH is necessary for the structural integrity and the
secretory activity of adrenal cortex.
• Follicle-stimulating Hormone (FSH)
• Follicle-stimulating hormone is a glycoprotein made
up of one α-subunit and a ß-subunit. The α-subunit
has 92 amino acids and ß-subunit has 118 amino
acids. The half-life of FSH is about 3 to 4 hours.
• In males, FSH acts along with testosterone and
accelerates the process of spermeogenesis
• In females FSH:
• 1. Causes the development of graafian follicle
from primordial follicle
• 2. Stimulates the theca cells of graafian follicle
and causes secretion of estrogen
• 3. Promotes the aromatase activity in granulosa
cells, resulting in conversion of androgens into
estrogen
 Luteinizing Hormone (LH)
• LH is a glycoprotein made up of one a-subunit and one ß-
subunit. The a-subunit has 92 amino acids and ß-subunit has 141
amino acids. The half-life of LH is about 60 minutes.
• In males, LH is known as interstitial cell-stimulating hormone
(ICSH) because it stimulates the interstitial cells of Leydig in
testes. This hormone is essential for the secretion of
testosterone from Leydig cells.
• In females, LH:
• 1. Causes maturation of vesicular follicle into graafian follicle
along with follicle-stimulating hormone
• 2. Induces synthesis of androgens from theca cells of growing
follicle
• 3. Is responsible for ovulation
• 4. Is necessary for the formation of corpus luteum
• 5. Activates the secretory functions of corpus luteum.
• Prolactin
• Prolactin is a single chain polypeptide with 199
amino acids.
• Its half-life is about 20 minutes. Prolactin is
necessary for the final preparation of mammary
glands for the production and secretion of milk.
• Prolactin acts directly on the epithelial cells of
mammary glands and causes localized alveolar
hyperplasia.
 POSTERIOR PITUITARY OR NEUROHYPOPHYSIS
• Posterior pituitary consists of three parts:
• 1. Pars nervosa or infundibular process
• 2. Neural stalk or infundibular stem
• 3. Median eminence.
• Pars tuberalis of anterior pituitary and the neural
stalk of posterior pituitary together form the
hypophyseal stalk.
• Posterior pituitary is made up of neural type of
cells called pituicytes and unmyelinated nerve
fibers.
 HORMONES OF POSTERIOR PITUITARY
• Posterior pituitary hormones are:
• 1. Antidiuretic hormone (ADH) or vasopressin
• 2. Oxytocin.
Source of Secretion of Posterior Pituitary Hormones
• Actually, the posterior pituitary does not secrete any
hormone.
• ADH and oxytocin are synthesized in the
hypothalamus.
• From hypothalamus, these two hormones are
transported to the posterior pituitary through the
nerve fibers of hypothalamo-hypophyseal tract, by
means of axonic flow.
• Proteins involved in transport of these hormones
are called neurophysins.
• In the posterior pituitary, these hormones are
stored at the nerve endings.
• Whenever, the impulses from hypothalamus
reach the posterior pituitary, these hormones are
released from the nerve endings into the
circulation. Hence, these two hormones are
called neurohormones.
 ANTIDIURETIC HORMONE
• Antidiuretic hormone (ADH) is secreted mainly
by supraoptic nucleus of hypothalamus. It is also
secreted by paraventricular nucleus in small
quantity.
• After secretion, it is transported to posterior
pituitary through the nerve fibers of
hypothalamo-hypophyseal tract, by means of
axonic flow.
• Antidiuretic hormone is a polypeptide containing
9 amino acids. Its half-life is 18 to 20 minutes.
• Antidiuretic hormone has two main functions:
• 1. Retention of water
• 2. Vasopressor action.
• 1. Retention of water
• Major function of ADH is retention of water by acting
on kidneys, hence its name of antidiuretic hormone.
• It increases the facultative reabsorption of water from
distal convoluted tubule and collecting ducts of the
kidney nephrons so that water enters the hypertonic
interstitium of the renal pyramids.
• The fluid that finally leaves the collecting duct (urine)
becomes concentrated and its volume decrease.
• In the absence of ADH, the distal convoluted tubule
and collecting duct are totally impermeable to
water.
• So, reabsorption of water does not occur in the
renal tubules and dilute urine is excreted. This leads
to loss of large amount of water through urine.
• This condition is called diabetes insipidus and the
excretion of large amount of water is called diuresis.
• ADH increases water reabsorption in tubular
epithelial membrane by regulating the water
channel proteins called aquaporins through V2
receptors.
 2. Vasopressor action
• In large amount, ADH shows vasoconstrictor
action. Particularly, causes constriction of the
arteries in all parts of the body. Due to
vasoconstriction, the blood pressure increases.

• ADH acts on blood vessels through V1A

receptors. However, the amount of ADH
required to cause the vasopressor effect is
greater than the amount required to cause the
antidiuretic effect.
 Control of ADH Secretion
• Potent stimulants for ADH secretion are:
• 1. Decrease in the extracellular fluid (ECF)
volume
• 2. Increase in osmolar concentration in the ECF.
• 3. Severe exercise
• Neurogenic states such as pain, surgical stress
and some emotions.
• Certain drugs e.g. nicotine, morphine and large
dose of barbiturates.
 Role of osmoreceptors in ADH control
• Osmoreceptors are the receptors which give response
to change in the osmolar concentration of the blood.
• These receptors are situated in the hypothalamus near
supraoptic and paraventricular nuclei.
• When osmolar concentration of blood increases, the
osmoreceptors are activated.
• In turn, the osmoreceptors stimulate the supraoptic
and paraventricular nuclei which send motor impulses
to posterior pituitary through the nerve fibers and
cause release of ADH.
• ADH causes reabsorption of water from the renal
tubules. This increases ECF volume and restores the
normal osmolarity.
 OXYTOCIN
• Oxytocin is a polypeptide having 9 amino acids.
• It has a half-life of about 6 minutes.
• It is secreted mainly by paraventricular nucleus of
hypothalamus and also secreted by supraoptic nucleus in
small quantity
• It is transported from hypothalamus to posterior pituitary
through the nerve fibers of hypothalamo-hypophyseal
tract. In the posterior pituitary, the oxytocin is stored in
the nerve endings of hypothalamo-hypophyseal tract.
• When suitable stimuli reach the posterior pituitary from
hypothalamus, oxytocin is released into the blood.
• Oxytocin is secreted in both males and females.
• It has a half-life of about 6 minutes
• In females, oxytocin acts on mammary glands and
uterus.
• Action of oxytocin on mammary glands
• Oxytocin causes ejection of milk from the
mammary glands. Ducts of the mammary glands
are lined by myoepithelial cells.
• Oxytocin causes contraction of the myoepithelial
cells and flow of milk from alveoli of mammary
glands to the exterior through duct system and
nipple.
• The process by which the milk is ejected from
alveoli of mammary glands is called milk ejection
reflex or milk letdown reflex. It is one of the
neuroendocrine reflexes.
• On pregnant uterus
• Throughout the period of pregnancy, oxytocin
secretion is inhibited by estrogen and progesterone.
• At the end of pregnancy, the secretion of these two
hormones decreases suddenly and the secretion of
oxytocin increases.
• Oxytocin causes contraction of uterus and helps in the
expulsion of fetus. During the later stages of
pregnancy, the number of receptors for oxytocin
increases in the wall of the uterus.
• Because of this, the uterus becomes more sensitive to
oxytocin. Oxytocin secretion increases during labor.
•
• At the onset of labor, the cervix dilates and the
fetus descends through the birth canal.
• During the movement of fetus through cervix,
the receptors on the cervix are stimulated and
start discharging large number of impulses.
• These impulses are carried to the
paraventricular and supraoptic nuclei of
hypothalamus by the somatic afferent nerve
fibers. Now, these two hypothalamic nuclei
secrete large quantity of oxytocin, which
enhances labor by causing contraction of uterus