HORMONES OF THE POSTERIOR

PITUITARY

The posterior pituitary is an extension of the hypothalamus and contains the axon terminals of magnocellular neurons
located in the supraoptic and paraventricular nuclei.
The neuropeptides produced by the magnocellular neurons, and consequently released from the posterior pituitary, are
oxytocin and AVP. As the axons leave the supraoptic and paraventricular nuclei, they give rise to collaterals, some of
which terminate in the median eminence.
These neuropeptides enter the systemic circulation through venous drainage
of the posterior pituitary into the intercavernous sinus and internal jugular
vein. In the systemic circulation, oxytocin and AVP circulate unbound. They
are rapidly cleared from the circulation by the kidney and, to a lesser extent,
by the liver and brain. Their half-life is short and is estimated to range
between 1 and 5 minutes
 1. Neurophysins

have an important role in the transport of AVP from the cell bodies of magnocellular neurons to their final release from
the posterior pituitary.

Impairment in hormone targeting leads to retention of the mutated neuropeptide precursor in the endoplasmic reticulum of the
magnocellular neurons, and these cells progress to programmed cell death (apoptosis).

2. Oxytocin
The neuropeptide oxytocin is synthesized by magnocellular neurons in the supraoptic and paraventricular nuclei of the
hypothalamus and is released from the posterior pituitary into the peripheral circulation. The release of oxytocin is stimulated by
sucking during breast-feeding (lactation) and stretch of the cervix during childbirth (parturition).
• The suckling of the nipple of the lactating breast
also stimulates oxytocin release. The afferent
sensory signals elicit an increase in oxytocin
release into the circulation. Leading to milk
ejection by producing contraction of the
myoepithelial cells that line the alveoli and ducts
in the mammary gland
• In the pregnant uterus, oxytocin produces rhythmic smooth muscle contractions to help induce labor and to promote
regression of the uterus following delivery (uterine involution).
The effects of oxytocin in the pregnant uterus are augmented by a dramatic increase in sensitivity to the hormone during the
onset of labor. This increased sensitivity to oxytocin is caused by an increased density (upregulation) of oxytocin receptors in
the uterine muscle. Receptor levels can be 200 times greater at the onset of labor than in the non-pregnant uterus. Because
of this increase, levels of oxytocin that would normally not be effective can produce forceful

The increased number in oxytocin receptors, the increase number in gap junctions between smooth muscle cells,
and the increased synthesis of prostaglandins enhance the responsiveness of the uterine muscle.

All of these factors enhance myometrial contractile activity in

response to oxytocin
 CONTROL OF OXYTOCIN RELEASE

.
Before the oxytocin neurons can secrete oxytocin, they must be released from inhibition by other neurons containing endogenous
opioids, nitric oxide, and -aminobutyric acid. This modulation of oxytocin release is partly caused by the declining blood levels
of progesterone and increasing levels of estrogen during late pregnancy. The neurotransmitters involved in stimulating oxytocin
release are thought to be acetylcholine and dopamine.
• The mechanical stimulation of the uterine cervix by the fetus near the end of gestation is stimulus for oxytocin release
• Oxytocin release is also stimulated by the forceful contractions of the uterus during the fetal expulsion reflex
• The contractile activity of the uterus acts through positive feedback mechanisms during parturition to stimulate oxytocin
neurons
• Breast-feeding generates sensory impulses that are transmitted to the spinal cord and then to the oxytocin-producing
neurons in the hypothalamus. The information transmitted by these sensory afferents produces intermittent synchronized
burst-fi ring of oxytocin neurons, resulting in pulsatile release of oxytocin and increases in blood oxytocin concentrations.
• In addition to its secretion from neurohypophysial terminals in the posterior pituitary, oxytocin is released within the
hypothalamic supraoptic and paraventricular nuclei. The function of this intrahypothalamic release of oxytocin is to
• control the activity of oxytocin neurons in an autocrine fashion by a positive feedback mechanism, increasing the
neurohypophysial release of oxytocin.

The release of oxytocin is inhibited by severe pain, increased body temperature, and loud noise.
 Arginine Vasopressin (AVP)
Antidiuretic hormone (ADH)

• The principal effect of AVP is to increase water reabsorption by enhancing permeability to water in the distal convoluted
tubules and the medullary collecting ducts in the kidney.

• Increases vascular resistance.

This function of AVP may be important during periods of severe lack of responsiveness to other vasoconstrictors, as may occur
during severe blood loss (hemorrhagic shock) or systemic infection (sepsis).

A RGININE V
ASOPRESSIN Receptors:

1. V 1 R . It is foundin the liver, smooth muscle, brain, and adrenal glands. The vasopressor effects of AVP are mediated through
the V 1 R.
2. V 2 R is expressed in the kidney. Binding of AVP to the V 2 R. The water re-absorptive effects of AVP are mediated through the
V 2R
 Tubular Effects of AVP
DT
PT
H2O
Cortex

CCD

TAL H2O
Outer
Medulla

Inner H2O
Medulla

IMCD
 Cellular Actions of AVP on Principal Cells of Collecting Duct

Tubular
Blood
fluid
AVP
H20 vaptans
H20 5 AMP
--Phospho-
diesterase V2 AVP
GS
Fusion of
vesicles containing PKA cAMP
water channels
AC
ATP
(aquaporin 2) GI
Phosphoproteins

H20
H20

Basolateral cell
membrane
Apical cell
membrane Capillary basement
membrane
 AVP Responses to Changes in Plasma Osmolality

15
1400

Urine Osm (mOsm/kg)

1200
p[AVP] (pg/ml) 10
1000
800

5 600
400
200
0 0
270 280 290 300 310 10 1 2 3 4 5 10 15
pOsm (mOsm/kg) p[AVP] (pg/ml)

Intensity of thirst
8

0
280 300 320
pOsm (mOsm/kg)
 Osmolar and Volume Control of AVP Secretion

15 100

p[AVP] (pg/ml)

p[AVP] (pg/ml)
80
10
60

5 40

20

0 0
270 280 290 300 310 30 20 10 0
pOsm (mOsm/kg) 15 %Δ blood volume
15% decrease in or arterial pressure

p[AVP] (pg/ml)
volume/pressure
10

Normal

5
15% increase in
volume/pressure

0
270 280 290 300 310
pOsm (mOsm/kg)
 Factors Affecting AVP Secretion

Stimulation Inhibition
Extracellular fluid osmolality Extracellular fluid osmolality
increase decrease
Volume decrease Volume increase
Pressure decrease Ethanol
Pain
Nausea and vomiting
Stress
Drugs
Nicotine
Morphine
Barbituates
AVP also binds the V 1 receptor, expressed in
vascular smooth muscle, producing
contraction and increasing peripheral vascular
resistance

The hormone is known as vasopressin

because of these vasoconstrictor effects.
AVP release:
• Increase in plasma osmolarity (the most effective stimulus for release). Even in very small change.

• Decrease in blood volume .

• Dehydration produce loss of intracellular water from osmoreceptors which signals the AVP magnocellular neurons to
stimulate AVP release, even before sensation of thirst.

• Excessive fluid intake or IV fluid administration result in swelling and hyperpolarization of magnocellular neurons result in
decreased release of AVP.

• Decrease in blood pressure less than 10% or decrease in blood volume which detected by pressure sensitive receptor.
 Disorders of AVP Production:
 Deficiency of ADH release results in DI, a clinical syndrome resulting from the inability to form concentrated urine.

 Excess AVP release is known as syndrome of inappropriate antidiuretic hormone secretion (SIADH).

Diabetes insipidus
• Decreased arginine vasopressin release, Neurogenic (central or hypothalamic)
• Decreased renal responsiveness to arginine vasopressin, Renal (nephrogenic) DI results from renal insensitivity to the
antidiuretic eff ect of AVP.