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Pituitary Hormones 1&2

6th July, 2017


Batch 2015/2020

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Contents
1. Actions of growth hormone
2. Regulation of secretion of growth hormone
3. Effects of hypo- and hypersecretion of
growth hormone
4. Actions of prolactin
5. Regulation of prolactin and effects of
abnormal secretion of the hormone

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Recall :
1. Hormone definition, classification, & mechanism of actions.
2. The relation between neural and endocrine physiology as it
pertains to the hypothalamus and pituitary.
3. Neuron-neuron interactions, hypophysiotropic hormones, and the
concepts of feedback and feed forward loops.
4. The characteristics and actions of the hypophysiotropic hormones:
thyrotropin releasing hormone (TRH); gonadotropic releasing
hormone (GRH); somatostatin; corticotropin releasing hormone
(CRH); growth hormone releasing hormone (GHRH); prolactin
inhibiting factor (PIF) and releasing factor (PRF).
5. Effects of these various hormones of pituitary gland: Antidiuretic
hormone, [ recall Renal Block], ACTH, TSH, Prolactin, Oxytocin,
Gonadotropins [ recall RPD Block]

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The endocrine system
Includes the organs of the body that secrete
hormones directly into body fluids such as
blood
Regulates chemical reaction in cells and
R
therefore control functions of the organs, E
tissues, and other cells S
P
O
Target N
Glands Chemicals
organs S
E
S
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Endocrine System vs Neuronal System
Differences
1. In nervous system, neurons
Similarities
communicate with adjacent
1. Chemicals are stored and
neurons; in hormones messages are
released sent long distances
2. Release of chemicals is due to 2. Neural messages induce rapid
stimulation response compared to hormones
3. Many different hormones & which have slower messages
neurotransmitters 3. Neural messages follow the all
4. Both systems react w/specific or none principle; hormonal
receptors messages are graded in strength
5. Second meesenger involved in 4. Neural messages can be
both directed as observed in behavior;
hormonal messages are primarily
involuntary (cannot be directed)

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Major Glands of the Endocrine System

Hypothalamus
Pituitary
Thyroid
Parathyroid
Pancreas -
endocrine
Adrenal
Gonads: Ovaries
& Testes
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Exceptions

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Hormones are Extremely Powerful

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Parvocellular - PVN
Arcuate nucleus
Magnocellular PVN, SON

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Pituitary
Anterior Pituitary Posterior Pituitary
- derived during - derived from nervous tissue
embryological development - two protein hormones
from the roof of the mouth released: oxytocin &
- connected to the vasopressin
hypothalamus by a portal ________________________
system (hypothalamic- Two Important Points:
pituitary portal system) Hormones released from the
- most of the hormones are posterior pituitary are
released from the anterior synthesized in the hypothalamus.
pituitary
Hormones released from the
anterior pituitary are dormant
unless directed to be released by
the hypothalamus via Releasing
Factors.
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Pituitary & all Hormones are Under the
Control of the Hypothalamus
Hypothalamus

RF Hormone

Anterior Pituitary Posterior Pituitary

SH Hormone

Target Organs Target Organs

RF = Releasing Factor SH = Stimulating Hormone


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Feedback Mechanisms

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Ultimately,what controls the
endocrine system?
Higher Brain Areas
Our emotions
Our perceptions
Hypothalamus
Our cognitions
Our experiences
Our behavior Pituitary
Our response to
the environment Endocrine Glands
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Pituitary - 1
Anterior
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Pituitary Gland
The pituitary gland lies
at the base of the skull
and is housed within a
bony structure called the
sella turcica.

Its weight in normal


adults is about 500 mg
(0.02 ounce).

The gland is attached to


the hypothalamus by the
pituitary stalk,
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Anterior Pituitary Hormones
Seven hormones are secreted by groups of anterior pituitary
cell: TSH, FSH, LH, ACTH, MSH, GH, prolactin.

Anterior pituitary hormones can be organized into three


groups based on chemical and functional similarities:
TSH, FSH, LH (same -chain and different -chain);
ACTH and MSH (derived from proopiomelanocortin, POMC);
GH and prolactin (straight amino acid chain, about 75%
same).

Growth Hormone is the main regulator of postnatal


growth and development, and prolactin is the major
hormone responsible for milk production.
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Growth Hormone
Cells of body in response to growth hormone
i. During childhood GH is at maximum
1. Too little and there will be a small person
2. Too much and there will be gigantism,
often accompanied by acromegaly
(continued growth of extremities of
bones)
a. enlarged hands, feet, jaw, nose, and
eye sockets (orbits)

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All hormones utilize feedback loops:
Autocrine response Same as the
autoreceptors, both communicate and
terminate release

Note similarity to the CNS:


Autoreceptors in the CNS the receptors on
presynaptic cell that are sensitive to its own
NT

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Growth Hormone (GH)

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Growth Hormone and Insulin-Like
Growth Factor 1

GH, or somatotropin, is responsible


for the growth of almost all cells and
tissues.

This can be done by both a DIRECT


and an INDIRECT effect.

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Direct effects
(anti-insulin effects)
such as increased lipolysis and
increased glucose mobilization.

The direct growth promoting actions of


include
Induction of insulin resistance in peripheral tissues
Hyperinsulinism
Lipolysis 30-50%
Direct effect on
Ketogenesis
growth plate
Hyperglycemia
50-70%
Sodium and water retention Through IGF-1
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Enhanced
utilization
of fat by
stimulating
triglyceride
breakdown
and
oxidation in
adipocytes.

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For SELF Study

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A properly functioning interaction among insulin,
GH, and IGF-I is critical for normal growth and
metabolism.

GH requires insulin for expression of its receptors,


which activate IGF-I, leading to the mediation of
some, but not all, of the actions of GH.

The synergy between insulin and GH that results


in the stimulation of growth and development of
bone and muscle mass occurs at lower GH
concentrations than would be required in the
absence of IGF-I.
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Mechanism of Action
GH binding to two GHRs
dimerization of GHR

activation of the GHR-associated


JAK2 tyrosine kinase,

+
tyrosyl phosphorylation of both JAK2 and GHR.

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Recruit and/or activate a variety of
signaling molecules

MAP kinases insulin receptor phosphatidylinositol 3'


substrates phosphate kinase
diacylglycerol
protein kinase C

intracellular calcium Stat transcription factors

GH-induced changes in enzymatic activity,


transport function, and gene expression

changes in growth and


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metabolism.
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The Regulation of GH secretion

(IGF-1)

The control of GH release occurs


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levels
Stomach Ghrelin binds
to receptors on
somatotrophs stimulates
secretion of growth
hormone
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Peak levels of 20 ng/mL to 25 ng/mL
occur during sleep a major physiological
regulator of GH release.
In addition, ghrelin, secreted primarily
from the stomach during fasting,
stimulates GH release by interacting with
the GH secretagogue receptor (GHSR).
Several other factors, such as stress,
puberty, obesity, and a variety of
signaling molecules modulate GH release,
resulting in a complex network of the
regulation of GH secretion

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GH during puberty

Increased GH secretion is manifested as an


increase in the pulse amplitude of the nocturnal
sleep-entrained secretion.
This increased GH levels insulin resistance
which is compensated by increased insulin
secretion, which augments the growth-promoting
effects of GH alone and in conjunction with sex
steroids, produces the final physical shape and
the differentiation between male and female
growth.

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Rates of glycerol production in pubertal >
prepubertal children.
A significant increase in lipolysis
Fatty acid oxidation over glucose oxidation
is also significantly increased in puberty as
compared to prepuberty.
This is accompanied by a drop in
circulating free fatty acids, as the fatty
acids produced by GH are metabolized,
sparing amino acids and glucose for other
effects including growth.

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Secretion - pulsatile
Stimulation Inhibit
Drcreased blood glucose Increased BGL
Decreased blood free Increased FFA
fatty acids Aging
Starvation or fasting, Obesity
protein deficiency Somatostatin
Trauma, stress, Exogenous growth
excitement hormone
Exercise Somatomedins [ IGF-1]
Testosterone
Deep sleep Adult plasma 1.6 3 ng/ml
GH-RH Child 6 ng/ml
Prolonged starvation as high as 50 ng/ml
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The diagnosis of acromegaly is confirmed by
demonstrating that GH secretion cannot be
suppressed below 1 ng/ml with a glucose load (oral
glucose tolerance test, OGTT).

One could also establish the diagnosis by frequent


sampling of GH and demonstrating the absence of
normal pulsatile GH secretion, but this is time consuming
and costly and not readily available in clinical practice.

Measurement of a single IGF-1 level may suggest the


diagnosis of GH excess but IGF-1 can be elevated in
physiologic conditions such as puberty or pregnancy and
falsely low in liver disease, renal disease, malnutrition or
with exogenous estrogen administration.

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Giantism is the result of
excessive growth hormone
secretion that begins in young
children or adolescents. It is a
very rare disorder, usually
resulting from a tumor of
somatotropes.
One of the most famous giants
was a man named Robert
Wadlow. He weighed 8.5
pounds at birth, but by 5 years
of age was 105 pounds and 5
feet 4 inches tall. Robert
reached an adult weight of 490
pounds and 8 feet 11 inches in
height. He died at age 22.

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JYOTI AMGE
24 years
24.7 inches tall
Achondroplasia

Is this the same as Pituitary


Dwarfism??

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PITUITARY DWARF

SHORT STATURE

Eleanor Simmonds, aged 13

ACHONDROPLASIA
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PROLACTIN

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Functions of prolactin
Induces lobuloalveolar growth of the
mammary gland. Alveoli are the clusters of
cells in the mammary gland that actually
secrete milk.

Stimulates lactogenesis or milk


production after giving birth. Prolactin,
along with cortisol and insulin, act together
to stimulate transcription of the genes that
encode milk proteins.
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Prolactin (PRL)

PRL is the major hormone responsible for milk production (lactogenesis) and
is involved in breast development.
PRL secretion is reciprocally controlled through the stimulatory actions of TRH
(and other yet to be identified hormones) and the inhibitory effect of dopamine.
In the nonlactating person, the effect of dopamine dominates so blood levels
of PRL are low. At puberty in the female, PRL enhances the ability of the
elevated levels of estrogen and progesterone to stimulate breast development.
During pregnancy, PRL secretion increases, and together with estrogen and
progesterone enhance the development of milk-producing cells in the breast.
Despite the high PRL levels, milk production does not occur because the high
levels of estrogen and progesterone act on the mammary gland to block the
lactogenic effect of PRL. At birth, the mothers blood levels of PRL, estrogen,
and progesterone fall. The act of suckling stimulates TRH (or some other
factor) and inhibits dopamine release producing a surge of PRL secretion,
which stimulates milk production.

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Clinical Manifestations of
Hyperprolactinemia
Women Men
Galactorrhea Galactorrhea
(30 - 80% of women) (< 10% of men)
Amenorrhea Impotence
Infertility Hypogonadism
Hirsutism Visual Field abnormalities
Extraoccular Muscle
Palsies
Headaches
Unless the plasma prolactin level is greater than 250
ng/ml (Normal < 20 ng/ml), other factors should be
considered as the Physiology:
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the hyperprolactinemia.52
The prolactinoma is the most common pituitary
adenoma.

Amenorrhea and impotence are due to the effect of


prolactin to inhibit GnRH secretion with the
subsequent reduction in LH/FSH secretion, as well as
interference with the actions of LH/FSH at the
gonads.

The result is a fall in estrogen or testosterone levels.

Prolactin may also stimulate androgen secretion from


the gonads and adrenal gland, resulting in hirsutism.

Because microadenomas are more commonly found in


women, symptoms due to compression of local
structures are generally found in men.
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Melanocyte-stimulating hormone,
MSH
Pro-opiomelanocortin
MSH
Stimulate melanocyte forming melanin to
deepen skin color.
Involved in releasing regulation of GH,
aldosterone, CRH, insulin, LH, etc.
Controlled by MIF (more) and MRF from
hypothalamus
MIF
MRF

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Trophic hormones
Anterior pituitary also secretes trophic hormone:
Thyroid-stimulating hormone (TSH)
Adrenocorticotropic hormone (ACTH);
Follicle stimulating hormone (FSH)
Done
already in
Luteinizing hormone (LH) RPD Block

All trophic hormones are taught/learnt along with the


respective glands/organs

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Desired Learning Outcomes
On completion of this lecture, you should be able
to:
1. describe the actions of growth hormone.
2. explain the regulation of secretion of growth
hormone.
3. describe the effects of hypo and hyper secretion
of growth hormone.
4. explain the actions of prolactin.
5. explain the regulation of prolactin and effects of
abnormal secretion of the hormone.

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Posterior Pituitary

Antidiuretic Hormone/ Vasopressin ADH


Oxytocin - OXY

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Contents:
1. Actions of vasopressin & oxytocin
2. Regulation of secretion of vasopressin &
oxytocin
3. Effects of hypo-and hyper secretion of
vasopressin & oxytocin

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Posterior
Pituitary
Neural tissue
Distal axons of hypothalamic magnocellular
neurons
The cell bodies of these axons are located in the
PARAVENTRICULAR and SUPRAOPTIC nuclei of
hypothalamus
PVN 80-90% vasopressin
Main neurotransmitters
Stimulatory glutamate
Inhibitory GABA --

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Vasopressin/ Oxytocin
Both synthesized as a part of precursor molecule
= nonapeptide + hormone specific neurophysin
Packaged in neurosecretory granules
Cleaved to the products during transport to the
posterior pituitary
Appropriate stimulus generation of AP
propagation to the posterior pituitary influx of
Ca++ neurosecretory granules fuse with cell
membrane exocytosis of contents into
perivascular space capillary system of Post Pit.

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At physiologic pH no binding of
these hormones to their
respective neurophysins and the
hormones circulate
independently in the
bloodstream.
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Mechanism of action
Antidiuretic hormone binds to receptors on cells in the
collecting ducts of the kidney and promotes reabsorption
of water back into the circulation. In the absence of
antidiuretic hormone, the collecting ducts are virtually
impermeable to water, and it flows out as urine.

Antidiuretic hormone stimulates water reabsorbtion by


stimulating insertion of "water channels" or aquaporins
into the membranes of kidney tubules. These channels
transport solute-free water through tubular cells and back
into blood, leading to a decrease in plasma osmolarity and
an increase osmolarity of urine.

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http://w3.palmer.edu/faruqui/figure_2.htm
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DR. PETER AGRE
Born: 30 January 1949,
Northfield, MN, USA

Affiliation at the time of the


award: Johns Hopkins
University School of Medicine,
Baltimore, MD, USA

NOBEL PRIZE IN 2003 -for the


discovery of water channels

Aquaporins are "the plumbing


system for cells

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Types of Aquaporins
Type Location[ Function

kidney (apically)
PCT
Aquaporin 1 Water reabsorption
PST
tDLH

kidney (apically)
ICT
Water reabsorption in
Aquaporin 2 CCT
response to ADH
OMCD
IMCD

kidney (basolaterally)
Water reabsorption and
Aquaporin 3 medullary collecting
glycerol permeability
duct

kidney (basolaterally)
Aquaporin 4 medullary collecting Water reabsorption
duct

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The collecting tubule is the site at which the final urine
concentration is determined. Antidiuretic hormone
(ADH, also called arginine vasopressin, AVP) controls
the permeability of this segment to water by regulating
the insertion of preformed water channels (aquaporin-
2, AQP2) into the apical membrane via a G protein-
coupled, cAMP-mediated process .

In the absence of ADH, the collecting tubule (and duct)


is impermeable to water, and dilute urine is produced.
ADH markedly increases water permeability, and this
leads to the formation of a more concentrated final
urine.

ADH also stimulates the insertion of urea transporter


UT1 molecules into the apical membranes of
medullary collecting tubule cells.
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Physiologic regulation
2 systems
Osmotic & Pressure/Volume
V1a receptors on blood vessels
V2 receptors on renal collecting duct epithelia
Non traditional effects
V3 [V1b]: VP stimulate ACTH release from Ant.
Pit.
V2 : stimulate production of factor VIII & vWF

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Vasopressin mainly in the regulation of water
homeostasis/ osmolality

Plasma VP much more sensitive to change in


osmolality
Only 1% increase in osmolality can induce release of
VP/ADH
10-15% increase in volume or pressure is required

Other influences :
Glucocorticoids inhibitory
Nausea & vomiting stimulatory
Important in pathologic conditions
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Volume & pressure regulation
Low pressure volume receptors
High pressure arterial
atria & pulmonary venous
baroreceptors- CS & AA
system
Normally inhibit
magnocellular neurons

When this tonic inhibition is


decreased, VP release results

effective
VP V1a receptors arterial and venous increase in the
on blood vessels constriction plasma volume
inhibition of VP release
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reestablished
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Major hormonal regulation to control volume
is
RAAS stimulates sodium reabsorption
by the kidneys

Baroreceptors and volume receptor


responses increased vasopressin release in
humans much less sensitive than the
osmoreceptors
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WHY IS THIS SO?

Study yourself

Discussion later in
Tutorials

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Osmotic regulation
Extracellular fluid
osmolality = ?????
Range closely
maintained
ADH [VP]
sensitive to changes
in plasma osmolality
Linear relationship

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How do you calculate plasma osmolality?

pOsm = 2x[Na+] + glu/18 + BUN/2.8

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Abnormal secretions
Diabetes Insipidus
Central
Nephrogenic

SIADH -syndrome of inappropriate


antidiuretic hormone secretion other name
??

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OXYTOCIN
Lactation

Parturition

Behavior

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Oxytocin
maternal behavior
Sociability in females/ pair bonding [love hormone]
Induces trust and empathy for in group mates
satiety an effect blunted in pregnancy so as to
increase food intake
Orgasm
evokes feelings of contentment, reductions in anxiety,
and feelings of calmness and security around the mate
modulate inflammation by decreasing certain
cytokines
effects on muscle contractibility facilitate sperm
and egg transport
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VP
stimulator of hypothalamo-pituitary-adrenal
axis
Behaving as a neurotransmitter in response to
stress
Studies have linked VP to memory

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Both sexes secrete oxytocin - what
about its role in males?
same regions of the hypothalamus as in females, and
also within the testes and perhaps other reproductive
tissues.
Pulses of oxytocin can be detected during ejaculation.

Current evidence suggests that oxytocin is involved in


facilitating sperm transport within the male
reproductive system and perhaps also in the female,
due to its presence in seminal fluid. It may also have
effects on some aspects of male sexual behavior.

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SDL
Non neural sources of Oxytocin

What type of receptors will Oxytocin have?


What is the second messenger system
involved in it?

Name the areas of the brain where OXY


Receptors are found to be expressed.
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Desired Learning Outcomes
On completion of this lecture, you should be
able to:
1. describe the actions of vasopressin &
oxytocin.
2. explain the regulation of secretion of
vasopressin & oxytocin.
3. describe the effects of hypo- and hyper
secretion of the hormones

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