Endocrinology

 Endocrinology is concerned with the study of the

biosynthesis, storage, chemistry, and physiological
function of hormones and with the cells of the
endocrine glands and tissues that secrete them.
 Endocrinology is the study of chemical
communication systems that provide the means to
control a huge number of physiologic processes.
 Endocrinology is a branch of biological science
dealing with the endocrine system and its specific
secretions called hormones.
 INTRODUCTION
I. Organization of Endocrine System
The functions of the body are regulated by the
nervous and the endocrine system.
The endocrine system consists of endocrine glands
and cells that secrete hormones in various tissues.
 Like other communication networks, endocrine systems
contain transmitters, signals and receivers that are called,
respectively, hormone producing cells, hormones and
receptors.
 Works with the nervous system to maintain
homeostasis
 Principal functions of the
endocrine system
 Maintenance of the internal environment in the
body (maintaining the optimum biochemical
environment).
 Integration and regulation of growth and
development.
 Control, maintenance and instigation of sexual
reproduction, including gametogenesis, coitus,
fertilization, fetal growth and development and
nourishment of the newborn.
 II. Endocrine vs. Nervous Syste
 Major communication systems in the body
 Integrate stimuli and responses to changes
in external and internal environment
 Both are crucial to coordinate functions of
highly differentiated cells, tissues and
organs
 Unlike the nervous system, the endocrine
system is anatomically discontinuous.
Nervous system

•The nervous system exerts

point-to-point control through
nerves, similar to sending
messages by conventional
telephone.

•Nervous control is electrical in

nature and fast.
 Hormones travel via the
bloodstream to target cells
•The endocrine system broadcasts its
hormonal messages to essentially all
cells by secretion into blood and
extracellular fluid.
•Like a radio broadcast, it requires a
receiver to get the message –
•in the case of endocrine messages, cells
must bear a receptor for the hormone
being broadcast in order to respond .
 Comparison to the Nervous
System
Nervous System Both Endocrine System
Neurotransmitters Communicate between Release hormones into
released at synapses cells using chemical bloodstream
signals that bind to
receptor molecules
Receptors on Precise Receptors on target
postsynaptic cells cells(proteins/glycoprotein
s)
Act within seconds Work to maintain Act from seconds to hours
homeostasis
Brief duration unless Brief duration or may last
neuronal activity for days
continues
 endocrine glands -Don't have ducts. Secrete
hormones internally into blood stream. The
secretions, known hormones, circulate all
over the body in the blood but may produce
effects only in selected sites.
 exocrine glands -Have ducts. Secrete
externally into ducts.
 Response vs. distance traveled
 Endocrine action: the hormone is distributed in blood and
binds to distant target cells.
 Paracrine action: the hormone acts locally by diffusing
from its source to target cells in the neighborhood.
 Autocrine action: the hormone acts on the same cell that
produced it.
 III. Transportation of Hormones
1, Endocrine, or telecrine: glands or
specialized cells release hormones into the
circulating blood that influence the function of
cells at another location in the body.
 Transportation of Hormones
2,Neuroendocrine: neurons
secrete substances
(neurohormones) that reach the
circulating blood and influence
the function of cells at another
location of the body.
 Transportation of Hormones
3. Paracrine, in which cells secret substances
that diffuse into the extracellular fluid and affect
neighboring cells.
 The first step in understanding endocrinology
is to explore the meaning of such terms as
hormone, receptor and target cell, and to
obtain an understanding of how chemical
communication is controlled.
 A cell is a target because it has a specific
receptor for the hormone

Most hormones circulate in blood, coming into contact with essentially

all cells. However, a given hormone usually affects only a limited
number of cells, which are called target cells. A target cell
responds to a hormone because it bears receptors for the hormone.

Receptor-. A target cell responds to a hormone because it

bears receptors for the hormone.
Hormone receptors are found either exposed on
the surface of the cell or within the cell,
depending on the type of hormone.
 A hormone (from Greek όρμή - "to set in motion")
 is a chemical messenger secreted from one cell
(or group of cells) to act on another cell (or group of
cells). All multicellular organisms produce hormones
(including plants)
 Chemical substances, produced in the body by
endocrine glands, that are transported by the blood to other
organs to stimulate their function.
 A chemical produced in one part of the body, which has its
effects on another part (target cells). Endocrine glands are the
sites of secretion. The bloodstream transports the hormones to
their target tissues. Hormones act as chemical messengers.
helping to regulate specific body functions.
 Hormones
 Function to:
– Help regulate metabolic processes
– Help regulate rates of chemical reactions
– Aid in transport of substances across
membranes
– Regulate water and electrolyte balances
– Play a vital role in reproduction, development,
and growth.
 Hormones
 Neurohormones –
 Neurohumors
 Para hormones
 Phyto hormones
 Pheromones
 NUEROENDOCRINE
 Neuroendocrine
Nerve stimulation --- skeletal muscle
Endocrine ---blood forming organs
Post. Pituitary , adrenal medulla –nervous
control
Neuroendocrine reflex – examples
1.Whitten effect – mice – estrus cycle 4-5 days
 317 mice –1st -43, 2nd 44, 3rd 146, 4th 42 ,28
did not met -Average 58
2.Bruce effect-effect of pheromones on the
pregnancy of rat.
3.Low tept. Increases thyroxin out put in rat
4.Induced ovulator – cat, camel
5.Letdown of milk
History
Arnold A Berthold
(1803-1861)
 In one of the first endocrine
experiments ever recorded,
Professor Arnold A. Berthold
of Gottingen did a series of
tests on roosters in 1849
while he was curator of the
local zoo.
 Ablation and replacement
•Bethold found that a rooster's comb is an
androgen-dependent structure. Following
castration, the comb atrophies, aggressive male
behavior disappears, and interest in the hens is
lost.
•Importantly, Berthold also found that these
castration-induced changes could be reversed by
administration of a crude testicular extract (or
prevented by transplantation of the testes).
Claude Bernard
(1813-1878)
Claude Bernard stated that the
endocrine system regulates the
internal milieu of an animal. The
“internal secretions” were
liberated by one part of the body,
traveled via the bloodstream to
distant targets cells. Circa 1854
Bernard's charge was to
demonstrate that medicine, in
order to progress, must be
founded on experimental
physiology.
 Endocrine system maintains
homeostasis
The concept that hormones acting on distant target
cells to maintain the stability of the internal milieu
was a major advance in physiological
understanding.
The secretion of the hormone was evoked by a
change in the milieu and the resulting action on
the target cell restored the milieu to normal.
The desired return to the status quo results in the
maintenance of homeostasis
Charles Edouard Brown-Séquard
(1817-1894)
 Brown-Sequard further piqued mainstream scientific
interest in the chemical contents of the testes with
his famous auto-experimentation. On June 1, 1889,
before the Sociète de Biologic in Paris, Brown-
Sequard reported that he had increased his
physical strength, mental abilities and appetite by
self-injection with an extract derived from the
testicles of dogs and guinea pigs
 Although never substantiated, this claim prompted
researchers around the world to pursue the new
field of organotherapy
 Ernest Henry Starling
(1866-1927)
 Besides "his" law of the heart, Starling discovered
the functional significance of serum proteins.
 In 1902 along with Bayliss he demonstrated that
secretin stimulates pancreatic secretion.
 In 1924 along with E. B. Vernay he demonstrated
the re absorption of water by the tubules of the
kidney.
 He was the first to use the term hormone
 Pende was the first to use the term
endocrinology
 Banting & Best (1921) prepared extract of Dog
pancreas -- reduced blood sugar of
experimental animals
 Abel (1926) prepared insulin in crystalline form
 Stockard & Papanicabaou (1917) studied
estrus cycle in guinea pigs.
 Allen (1922) in rats & Mice
 Corner & Allen (1929) prepared extracts of
corpora leutea that effectively maintained
pregnancy in overectomized rabbits. This is now
called progesterone.
 David et al. (1935) prepared crystalline
hormone from testes called as testosterone.
 Research on pituitary hormones took a slow
pace due to difficulty in removing pituitary
without damaging brain
 Stricker & Grueter (1928) indicated that ant. Pit.
Is essential for initiation and maintenance of
milk secretion.
 White et al (1937) prepared crystalline
 Methods of study endocrinology
 1. Surgical ablation.
 2. Chemical ablation. Alloxan –B cells ,
radioactive iodine---thyroid , Amphenone –
adrenal cortex
 3. Replacement therapy a. trasplantation of the
gland . B. injection of extract of the gland . C.
administration of the hormone produced by
gland or prepared syntheticaly.
 Chemical extraction
 Isotopeic tracer method
 In vitro techniques
 Classification of Hormones
1. Proteins and Polypeptides, including hormones
secreted by the anterior and posterior pituitary
gland, the pancreas (insulin and glucagon), the
parathyroid gland (parathyroid hormone), and many
others.
2. Steroids secreted by the adrenal cortex (cortisol
and aldosterone), the ovaries (estrogen and
progesterone), the testes (testosterone), and the
placenta (estrogen and progesterone)
3. Derivatives of the amino acid tyrosine,
secreted by the thyroid (thyroxine and
triiodothyronine) and the adrenal medullae
(epinephrine and norepinephrine)
4. Fatty Acid Derivatives .
 Classes of hormones
 
 The hormones fall into two general classes
based on their solubility in water.
The water soluble hormones are the
catecholamines (epinephrine and
norepinephrine) and peptide/protein hormones.
The lipid soluble hormones include thyroid
hormone, steroid hormones and Vitamin D3
 Types of receptors
 Receptors for the water soluble hormones are
found on the surface of the target cell, on the
plasma membrane.
 These types of receptors are coupled to various second
messenger systems which mediate the action of the
hormone in the target cell.
 Receptors for the lipid soluble hormones reside in
the nucleus (and sometimes the cytoplasm) of the
target cell.
 Because these hormones can diffuse through the lipid
bilayer of the plasma membrane, their receptors are
located on the interior of the target cell
Hormones and their receptors
Hormone Class of Location
hormone

Amine Water-soluble Cell surface

(epinephrine)

Peptide/protein Cell surface

Water soluble
Amine
(thyroid Lipid soluble Intracellular
hormone)
Steroids and Lipid Soluble Intracellular
Vitamin D
 Hormone Receptors

 Surface

 Intracellular
VI. Mechanisms of Hormonal Action
The first step of a hormone’s action is to bind to specific
receptors at the target cell.
Locations for the different types of hormones:
1) On the surface of the cell membrane.
protein, peptide, and catecholamine hormones
2) In the cell cytoplasm.
steroid hormones
3) In the cell nucleus.
thyroid hormones (T3 and T4)
 1.Second Messenger Mechanisms for
Mediating Intracellular Hormonal Functions
 Hydrophilic hormones
(proteins, peptides
and catecholamine)
 --bind the receptors
on the membrane,
 --activate some
enzyme on the
membrane,
 -- regulate the
concentration of some
messengers (second
messengers) in the
cytoplasm. .
 Examples of Hormones Which Utilize
Second Messenger
This System

Epinephrine and norepinephrine,

Cyclic AMP
Protein kinase activity
glucagon,
luteinizing hormone, follicle stimulatin
g hormone
, thyroid-stimulating hormone,
calcitonin, parathyroid hormone,
antidiuretic hormone
Insulin, growth hormone, prolactin,
oxytocin, erythropoietin, several
growth factors

Epinephrine and norepinephrine,

angiotensin II, antidiuretic hormone,
Calcium and/or phosphoinositides
gonadotropin-releasing hormone,
thyroid-releasing hormone.

Cyclic GMP Atrial naturetic hormone, nitric oxide

One mechanism of non-steroid hormones. 1.) Body fluids carry nonsteroid hormone molecules to
target cell. Where 2.) they combine with receptor molecules on the cell membrane. 3.) This
activates molecules of adenylate cyclase, which 4.) catalyze conversion of ATP into cyclic
adenosine monophosphate (cAMP) 5.) The cAMP promotes a series of reactions leading to the
cellular changes associated with the hormone’s action.
2. Hormones That Act Mainly on the Genetic
Machinery of the Cell
(1)Steroid
hormones
increase protein
synthesis
(2) Thyroid
hormones
increase gene
transcription in
the cell nucleus
Steroid hormones. 1.) A steroid hormone crosses a cell membrane and 2.) combines with a
protein receptor, usually in the nucleus.3.) The hormone-receptor complex activates synthesis of
specific messenger RNA (mRNA) molecules. 4.) The mRNA molecules leave the nucleus and
enter the cytoplasm 5.) where they guide synthesis of the encoded proteins.
 Properties of the hormone effect
1. Specificity
The special feature of the the target cells is the
presence of receptors which can “attract” and
interact with the hormone.
The receptors may be present either on the
plasma membrane, or in the cytoplasm, or in the
nucleus.
These receptor molecules are protein in nature
and may contain carbohydrate or phospholipid
moieties.
 6. Interaction Between the Hormones
(1) Synergistic effects. When two or more hormones work
together to produce particular result their effect are said to
be synergistic.
These effects may be additive or complementary.
Additive: Same effect of the hormones on one target
organ, for example, epinephrine and norepinephrine on the
heart rate
Complementary: Work on different stages of a
physiological procedure, for example, FSH (initiation) and
testosterone (maintenance) on spermatogenesis
(2) Permissive effect. A hormone is said to have a
permissive effect on the action of a second
hormone when it enhances the responsiveness of a
target organ to the second hormone or when it
increases the activity of the second hormone.
Estrogen – Expression of progesterone receptors on
uterus – progesterone effect on the uterus.
Glucocorticoids – effects of catecholamines on
cardiovascular system
(3) Antagonist Effects. In some situations the
actions of one hormone antagonize the effects of
another.
Lactation during pregnancy is prevented because the
high concentration of progesterone in the blood
inhibits the milk secretion and action of prolactin.
 Agonist vs. Antagonist
 Agonists are molecules that bind the receptor and
induce all the post-receptor events that lead to a
biologic effect. In other words, they act like the
"normal" hormone, although perhaps more or less
potently
 Antagonists are molecules that bind the receptor
and block binding of the agonist, but fail to trigger
intracellular signaling events
 Feedback Control of Hormone
Production
Feedback loops are used
extensively to regulate
secretion of hormones in the
hypothalamic-pituitary axis.
An important example of a
negative feedback loop is seen
in control of thyroid hormone
secretion
GnRH
Prolactin

P4 (-)

FSH LH
Ox
yto
cin

Inhibin
(-)

Estradiol (+)
P4 P4
iol

PGF2
rad
Est
 Feedback control
 Negative feedback is most common: for example,
LH from pituitary stimulates the testis to produce
testosterone which in turn feeds back and inhibits
LH secretion
 Positive feedback is less common: examples
include LH stimulation of estrogen which
stimulates LH surge at ovulation
 Negative Feedback:
– A gland is sensitive to the concentration of a
substance it regulates.
– When concentration reaches a certain high
point, it inhibits the gland
– Inhibited gland releases less hormone,
controlled substance level also decreases.
– Maintains relatively stable hormone
concentrations.

Animation of Positive
and Negative Feedb
ack
Negative Feedback:
 Neural control
 Neural input to hypothalamus stimulates
synthesis and secretion of releasing factors
which stimulate pituitary hormone
production and release
 Chronotropic control
 Endogenous neuronal rhythmicity
 Diurnal rhythms, circadian rhythms (growth
hormone and cortisol), Sleep-wake cycle;
seasonal rhythm
Negative feedback effects of cortisol
 Substrate-hormone control
 Glucose and insulin: as glucose increases it
stimulates the pancreas to secrete insulin
 Calcium and Paratharmone: decrease in
blood calcium causes increase in
paratharmone output which intern mobilizes
calcium from skeleton.
 Control of Hormonal Secretions
 Precisely regulated.
 Continually excreted in urine and broken
down by the liver.
 Biological Assay of Hormone
 It is the method of estimation of the
concentration of a hormone, depending
upon some unique biological alteration that
it produces e. g .
 Insulin lowers blood glucose level
 Androgens produce the growth of capon’s comb
 Estrogens cornify the vaginal epithelium of rodents
 MSH causes dispersion of melanin granules in the
melanophores of frog’s skin
 Thyrotrophin induce specific changes in the structure
thyroid.
 Parathyroid hormone raises blood calcium level in
parathyroidectomised animal
 Limitations :
 Changes should be produced exclusively by a particular
hormone under rigidly controlled conditions, --- elevation of
blood sugar level can not be a measure of epinephrine
because hormones of adrenal cortex , glucagon etc. also
do the same job.
 The structural / functional changes should be measured
objectively with instruments instead of subjective
observations.
 The response may also depend upon the route of
administration
 It also depends upon the strain of animal, sex, age and
general health.
 Other methods
 RIA
 ELISA
 Endocrine Glands
 Hypothalamus
 Pituitary
 Thyroid
 Adrenal
 Kidneys
 Ovaries
 Testis
 Pancreas
 Pineal
 Digestive Tract
Hypothalamus and pituitary gland
The pituitary gland is attached to the hypothalamus and lies in the stella turcica of the
sphenoid bone.
Hypothalamus and pituitary gland
 Hypothalamus and Pituitary
 The hypothalamus-pituitary unit is the most
dominant portion of the entire endocrine
system.
 The output of the hypothalamus-pituitary
unit regulates the function of the thyroid,
adrenal and reproductive glands and also
controls somatic growth, lactation, milk
secretion and water metabolism.
 Major hormones and systems
 Top down organization of endocrine system.
 Hypothalamus produces releasing hormones /
factors that stimulate production of anterior
pituitary hormone which act on peripheral
endocrine gland to stimulate release of third
hormone
– Specific examples to follow
 Posterior pituitary hormones are synthesized in
neuronal cell bodies in the hypothalamus and are
released via synapses in posterior pituitary.
– Oxytocin and antidiuretic hormone (ADH)
 Hypothalamus and Pituitary
 Pituitary function depends on the hypothalamus
and the anatomical organization of the
hypothalamus-pituitary unit reflects this
relationship.
 The pituitary gland lies in a pocket of bone at the
base of the brain, just below the hypothalamus to
which it is connected by a stalk containing nerve
fibers and blood vessels. The pituitary is
composed to two lobes-- anterior and posterior
I. Anatomical and
Functional
Connection
Between the
Hypothalamus
and Pituitary
(hypothalamo-
hypophyseal
portal system and
tract)
 Hypophyseal portal system

 All blood entering the portal system will

reach the intended target cells before
returning to the general circulation
The Hypophyseal Portal System

Figure 18.7
 Hypothalamic releasing hormones /
factors for anterior pituitary hormones

 Travel to adenohypophysis via hypophyseal-portal

circulation
 Travel to specific cells in anterior pituitary to
stimulate synthesis and secretion of trophic
hormones
 Hypothalamic releasing hormones
Hypothalamic releasing hormone Effect on pituitary

Corticotropin releasing hormone (CRH) Stimulates ACTH secretion

41 aa
Thyrotropin releasing hormone (TRH) Stimulates TSH and Prolactin secretion
3 aa
Growth hormone releasing hormone Stimulates GH secretion
(GHRH) 44 aa
Somatostatin 14 aa Inhibits GH (and other hormone)
secretion
Gonadotropin releasing hormone (GnRH) Stimulates LH and FSH secretion
a.k.a LHRH 10 aa
Prolactin releasing hormone (PRH) Stimulates PRL secretion

Prolactin inhibiting hormone (dopamine) Inhibits PRL secretion

 Characteristics of hypothalamic
releasing hormones
 Secretion in pulses
 Act on specific membrane receptors
 Transduce signals via second messengers
 Stimulate synthesis of pituitary hormones
 Stimulate release of stored pituitary hormones
 Stimulates hyperplasia and hypertrophy of target
cells
 Regulates its own receptor
Hypothalamus and
posterior pituitary

Midsagital view illustrates

that magnocellular neurons
paraventricular and
supraoptic nuclei secrete
oxytocin and vasopressin
directly into capillaries in
the posterior lobe
Hypothalamus and
anterior pituitary
Midsagital view
illustrates parvicellular
neurosecretory cells
secrete releasing factors
into capillaries of the
pituitary portal system
at the median eminence
which are then
transported to the
anterior pituitary gland
to regulate the secretion
of pituitary hormones.
Hypothalamus
and anterior
pituitary
 neocortex

Reituclar
activating
substance
Thalamus Limbic
system
Optical
system
Regulation
Sleep/
wake
pain Emotion, fright,
rage, smell vision
of
Heat regulation
(temperature)
Energy
regulation
(hunger,
Autonomic
regulation
(blood pressure
Hypothalamus
BMI) etc)
Water balance (blood
Metabolic rate, stress
volume, intake--thirst,
response, growth,
output—urine volume)
reproduction, lactation)

Anterior
pituitary
posterior hormones
pituitary
hormones
 The hypophyseal portal blood system connects the
hypothalamus with anterior pituitary and is the route
by which hormones of the hypothalamus reach the
anterior pituitary.
 The hypothalamic hormones are released from
terminals of axons (nerve fibers) into blood vessels
which serve the anterior pituitary
 The area of the hypothalamus which receive
releasing factors are median eminence and the
pituitary vessels which receive releasing factors is the
hypophyseal portal vessels.
 Also, a portion of the venous return from the anterior
pituitary is by way of the hypothalamus.
 This permits a direct, short-loop feedback system
whereby hormones of the anterior pituitary may help
regulate release of hormones from the hypothalamus.
 HYPOTHALMUS

 The posterior
pituitary is an
extension of the
hypothalamus.
 Axons from
neurosecretory
cells in the
hypothalamus
extends down into
the posterior
pituitary
 HYPOTHALAMIC HORMONES
 Structure
– 3 to 44 amino acids
 Function
– release of ‘tropic’ hormones from ant. Pit.
HYPOTHALAMIC HORMONES

– Hypothalamus
 ‘master of reproduction’
 neural control
– hypothalamus  nerve cells  hypothalamic
nuclei
– neurohormones (neuropeptides)
 Oxytocin & Vasopressin

 other releasing hormones

 HYPOTHALAMO-HYPOPHYSEAL PORTAL
SYSTEM
HYPOTHALAMUS

Releasing Hormone

Primary Portal Plexus

(in pituitary stalk)

Releasing Hormone

Secondary Portal Plexus

(in anterior pituitary gland)

Tropic Hormone from Ant
Pit
 Anterior pituitary: adenohypophysis
 Anterior pituitary: connected to the
hypothalamus by the superior hypophyseal
artery.
 The anterior pituitary is an amalgam of
hormone producing glandular cells.
 The anterior pituitary produces six peptide
hormones: prolactin, growth hormone (GH),
thyroid stimulating hormone (TSH),
adrenocorticotropic hormone (ACTH),
follicle-stimulating hormone (FSH), and
luteinizing hormone (LH).
Hypothalamus/Pituitary
Axis
 Chromophilic cells ( 50 % )
Acidophils (40%) Cells that contain the protein hormones:
Somatotropes ( 25%) which produce growth hormone
Lactotropes ( 15%) which produce prolactin

Cells that contain the glycoprotein hormones:

Thyrotropes which produce thyroid stimulating hormone
Gonadotropes which produce luteinizing hormone and follicle-stimulating
Basophils ( 10%) hormone
Corticotropes which produce adrenocorticotrophic hormone & β Lipotropin
Due the high carbohydrate content of the hormones within acidophils, they
also stain bright purple with PAS stains.

These are cells that have minimal or no hormonal content. Many of the
chromophobes may be acidophils or basophils that have degranulated and
Chromophobes
thereby are depleted of hormone. Some chromophobes may also represent
stem cells that have not yet differentiated into hormone-producing cells.
 Major target
Glands Hormone
organ(s)
Major Physiologic Effects

Promotes growth (indirectly),

Liver, adipose
Growth hormone control of protein, lipid and
tissue
carbohydrate metabolism

Thyroid-stimulating Stimulates secretion of thyroid

Thyroid gland
hormone hormones
Anterior
Adrenocorticotropic Adrenal gland Stimulates secretion of
Pituitary
hormone (cortex) glucocorticoids

Prolactin Mammary gland Milk production

Luteinizing hormone Ovary and testis Control of reproductive function

Follicle-stimulating
Ovary and testis Control of reproductive function
hormone

Antidiuretic hormone Kidney Conservation of body water

Posterior
Pituitary
Stimulates milk ejection and
Oxytocin Ovary and testis
uterine contractions
ANTERIOR PITUITARY HORMONES
 PITUITARY HORMONES
ANTERIOR PITUITARY
– Prolactin
 protein
 female target – mammary cells
 maternal behavior (brain)
 lactation (milk synthesis)
– Adrenocorticotropic Hormone (ACTH)**
 corticosteroids from adrenal gland
– Thyroid Stimulating Hormone (TSH)**
 thyroxine (T4) & triiodothyronine (T3) from thyroid
– Somatotropin (STH)**
 bone growth, muscle accretion, lactation
Pituitary - GH
 via somatomedins
promotes longitudinal
growth
 anabolic protein
metabolism, lipolytic,
stimulates insulin
release, decreases
peripheral tissue
utilization of glucose
Pituitary - FSH, LH
 Kallmann’s
syndrome-
maldevelopement
olfactory lobes,
related
hypothalamic
lesions, hyposmia,
anosmia, isolated
Gn-RH deficiency
II. Physiological Function of Hormones Secreted
From Anterior and Posterior Pituitary
1.Growth Hormone ( GH),or STH
(1)Physiological functions of growth hormone.
1) Growth effect
Growth hormone stimulates cell division, especially in
muscle and epiphyseal cartilage of long bones.
The result is muscular growth as well as linear growth.
GH also stimulates growth in several other tissues,
e.g.
skeletal muscle, heart, skin, connective tissue,
liver, kidney, pancreas, intestines, adrenals and
parathyroids. But no effect on nervous tissues &
gonads .
Hypersecretion of GH leads to cause gigantism in
children and acromegaly in adult.
Hyposection of GH results in dwarfism during
childhood.
Effect of
hypophysectomy
on growth of the
immature rhesus
monkey.
Both monkeys
were the same
size and weight 2
years previously,
when the one on
the left was
hypophysectomiz
ed.
Effect of growth hormone treatment for 4 days on
the proximal tibial epiphysis of the
hypophysectiomized rat.
Note that increased width of the unstained cartilage
plate in the tibia of the right, compared with the
control in the left.
 Growth Hormone Excess

• in childhood leads to GIGANTISM

If an acidophilic tumor
occur after adolescence –
that is , after the epiphyses
of the lone bones have fused
with shafts
– the person cannot grow
taller,
but the soft tissue can
continue to grow and the
bones can grow in
thickness.
This condition is known as
acromegaly.
 Growth Hormone Excess

• in adulthood leads to ACROMEGALY

Receptor
mechanism of the
growth hormone
effect
GH
somatomedins
(SM) （ also
called insulin-like
growth factor, IGF)
in the liver
growth of bone and
other peripheral
tissues.
2) Metabolic effects of GH
A, On Protein metabolism
Enhance amino acid transport to the interior of the
cells and increase RNA translation and nuclear
transcription of DNA to form mRNA, and so
increase rate of protein synthesis.
GH also reduces the breakdown of cell proteins by
decreasing catabolism of protein.
B, On fat metabolism
Cause release of fatty acids from adipose tissue and
then increasing the concentration of fatty acids.
Therefore, utilization of fat is used for providing
energy in preference to both carbohydrates and
proteins.
C. On glucose metabolism
Decreases cellular uptake of glucose and glucose
utilization,
leads to increase of the blood glucose concentration.
(2) Regulation of GH secretion
The plasma concentration of GH changes with age. 5
– 20 years old, 6ng/ml; 20 – 40 years old, 3ng/ml; 40
–70 years old, 1.6ng/ml.
The change of GH concentration within one day.
1) Role of hypothalamus and feedback mechanism
- Hypothalamus

GRH + - SS
- -
Pituitary

GH
Liver

SM Target tissues

+ increase the secretion; - inhibit the secretion

2) Other factors that affect the GH secretion
A, Starvation, especially with severe protein
deficiency
B, Hypoglycemia or low concentration of fatty acids
in the blood
C, Exercise
D, Excitement
E, Trauma
2. Prolactin (PRL)
(1)Physiological function of PRL
1) On mammary gland : stimulate the development
and milk secretion ( initiation and maintenance )
In female, mammary gland development at puberty is
stimulated by estrogen, progesterone, growth
hormone, cortisol, insulin, thyroid hormones and
prolactin.
During pregnancy, great growth of mammary gland
tissues occurs by stimulation of estrogen,
progesterone and prolactin but estrogen and
progesterone inhibit the secretion of milk.
Immediately after the baby is born, the sudden loss
of estrogen and progesterone secreted by the placenta
allows the lactogenic effect of PRL to assume its
nature milk promoting role, initiating milk secretion.
After birth of the baby, the level of PRL secretion
returns to the normal level before pregnancy but each
time the mother nurses her baby causes a 10 to 20 fold
surge in PRL secretion that lasts for about 1 hour.
Lactation is maintained for nursing period.
2) Effect on sexual organs
In FEMALE, PRL combined with PRL receptors in
granulosa cells stimulates production of LH receptors.
Through LH receptors, LH promotes ovulation and
then formation of corpus luteum. (permissive effect)
In male, PRL promotes growth of prostate glands and
seminal vesicle, enhancing the effect of LH on the
interstitial cells producing testosterone.
(2) Regulation of PRL secretion
1) Hypothalamic hormones and feedback
mechanism

Hypothalamus: PIF PRF

- +
+
Anterior pituitary: Prolactin

+ increase the secretion; - inhibit the secretion

2) Milk rejection reflex

Sucking, tactile stimulation

Afferent nerve (somatic nerve)

Centers including spinal cord and hypothalamus

PRF secretion Oxytocin secretion

PRL secretion Myoepithelial cells contraction

of mammary glands

Milk production increase Milk flows

PROLACTIN

SECRETION
 Pituitary - Prolactin
 acts on prepared mammary tissue to initiate
and maintain lactation
 Bio assay – crop milk in pigeon
 In rodents ,maintain corpus luteum
 In birds synergistically with E2 produce
broody patches
 Pituitary - ACTH
 precursor proopiomelanocortin (POMC)
 melanotropins, β lipotropins & β-endorphin
 39 aa , 1-23 common, rest sp. Specific
 1-13 similar to α MSH
 circadian rhythm peaks am,
 stimulus, CRH- stress, hypoglycemia,
 CRH-feed back from glucocorticoids in
circulation
 action- adrenal cortex-zona reticularis &
faciculata & secrete glucocorticoids
 Pituitary - TSH
 glycoprotein hormone, thyrotophs cells, level
constant, two chains α &β
 stimulus, TRH
 feedback free T3
 c-AMP mediated
 action-early increased formation of colloid,
uptake of iodine, formation of T3 & T4
 action-late increased volume and number of
cells
 ANTERIOR PITUITARY
Follicle Stimulating Hormone (FSH)
 Glycoprotein Sialic acid essential for activity
 affects granulosa cells of ovary ,increase wieght
 causes folliculogenesis ,stimulates estradiol synthesis
 In male spermatogenesis with testosterone
 Growth of sertoli cells & production of ABP & Inhibin
 Increase LH receptor

Luteinizing Hormone (LH)

 Glycoprotein , Sialic acid not essential
 affects theca interna cells and luteal cells of ovary
 stimulates ovulation – formation of CL , secretion of
Progesterone
 stimulates testosterone production in the male (ICSH)
 Intermediate Lobe
 Absent in birds & Elephent
 POMC
 α MSH 13aa, β MSH 18 aa & ў MSH 12aa
 -------,-----,-------,-----------,---,---------------
_ 131 _55 to-44 1—39 42 --134

ў MSH ACTH β LPH

α MSH CLIP ўLPH β endorphin

(1-13) (18-39), (42-101) (104-134)

β MSH met enkephalin
(84-101) ( 104-108)
 Posterior Pituitary:
neurohypophysis
 Posterior pituitary: an outgrowth of the
hypothalamus composed of neural tissue.
 Hypothalamic neurons pass through the
neural stalk and end in the posterior
pituitary.
 The upper portion of the neural stalk
extends into the hypothalamus and is called
the median eminence.
Pituitary-Hypothalamic Relationship
The posterior pituitary, also known as the
neurohypophysis.
Two important peptide hormones that secreted
by the posterior pituitary,
ADH
(or vasopressin)
oxytocin
3. Synthesis and Release of Vasopressin (VP) and
Oxytocin (OXT)
Cells in neurohypophysis do not synthesize hormones
but act simply as supporting structure for nerve
fibers.
ADH / Vasopressin
 Pituitary - antidiuretic hormone
(ADH) (vasopressin)
 CNS osmoreceptors in supraoptic,
peraventricular nuclei of hypothalamus
– plasma amorality changes
 baroreceptors, aortic arch, carotid sinus, left
atrium
– CN IX, X
 renal action
– ADH increases permeability of H2O in DCT and CD
(1)Roles of ADH
 Antidiuretic hormone V2-receptor: collecting duct

1) Antidiuretic effect - Aquaporines 5 types

Aquaporines 1,2,3 in kidney
Vasopressor hormone V1-receptor:
vascular smooth muscle

Pressure effect. High concentration of ADH have a

potent effect of constricting the arterioles
everywhere in the body, raise the resistance blood
flow and blood pressure
Deficiency causes --- Diabetes insipidus
Vasopressin (VP), also called ADH, and oxytocin (OXT) are
initially synthesized in the cell bodies of the supraoptic and
paraventricuar nuclei of hypothalamus
and are transported down to the nerve endings in the
neurohypophysis by hypothalamic hypophyseal tract.
When nerve impulses are transmitted downward along the fibers
from nuclei, the hormone is immediately released from secretary
granules in the nerve endings by exocytosis and is absorbed into
adjacent capillaries
Precursor – Pro pressophycin
Neurophycin I 93 aa with oxytocin
Neurophycin II 95 aa with vasopressin
 Structure of oxytocin:

Oxy = rapid; tocos = labor, Synthesized in

both sexes, A neno peptide with a disulfide,
bridge joining aa 1 to aa 6, Dale, an English
pharmacologist, was the first to note that an
extract of dried bovine pituitary gland
caused contraction of uterus.

Pre-prooxyphysin Signal Peptide OXT Neurophysin I

1 19 20 28 32 124 125
.

oxytocin (OXT)

Vasopressin (VP)

Arginine Vasopressin 3 – Phe 8 –Arg

Lysine Vasopressin (pig) 3 – Phe 8 –lys
Vasotocin (birds ) 8 –Arg
Oxytocin
 paraventricular & supraoptic nuclei of
hypothalamus
 stored in & released from post pit
 Nenopeptide
 oviductal contractions
 uterine contractions
 milk letdown (mammary alveolar contraction)
(2) Role of Oxytocin (OXT)
1) Effect on mammary glands.
Cause the contraction of the myoepithelial cells that
surround the outer walls of the alveoli of the
mammary glands, press the milk from the alveoli to
the duct and make it flow out --- milk ejection
Unconditioned and conditioned reflex
OXYTOCIN
2) Milk rejection reflex

Sucking, tactile stimulation

Afferent nerve (somatic nerve)

Centers including spinal cord and hypothalamus

PRF secretion Oxytocin secretion

PRL secretion Myoepithelial cells contraction

of mammary glands

Milk production increase Milk flows

2) Effect on uterus
OXT powerful stimulate the smooth muscle
contraction, especially that towards the end of
gestation & during coitus.
Action enhanced by E2 & Inhibited by P4
It is believed that OXT is at least partially responsible
for causing birth of the baby