THE POSTERIOR PITUITARY THE POSTERIOR PITUITARY GLANGLANDD

The posterior pituitary gland, also The posterior pituitary gland, also called called neurohypophysisneurohypophysis, is , is composed mainly of glial-like composed mainly of glial-like supporting cells called supporting cells called pituicytespituicytes . .

These do not produce hormone but These do not produce hormone but receive terminal nerve endings of receive terminal nerve endings of large large magnocellular neurons magnocellular neurons that that originate in the hypothalamusoriginate in the hypothalamus..

The posterior pituitary gland hormonesThe posterior pituitary gland hormones

Posterior pituitary gland releases 2 hormones:

1. Antidiuretic hormone (ADH), or arginine vasopressin (AVP). 2. Oxytocin

Both hormones are produced in hypothalamic nuclei: - Supraoptic nucleus (ADH + 1/6 oxytocin) - Paraventricular nucleus (Oxytocin + 1/6 ADH)

The posterior pituitary hormones –The posterior pituitary hormones – 1. ADH (vasopressin):1. ADH (vasopressin):

ADH activates (2) second messenger systems: 1. cAMP 2. IP3/Ca2+

Nerve tracts originate in the supraoptic and paraventricular nuclei of the hypothalamus. These tracts pass to the neurohypophysis through the pituitary or hypophyseal stalk.

The nerve endings are bulbous knobs that contain many secretory granules called herring bodies. These endings lie on the surfaces of the capillaries onto which they secrete two posterior pituitary hormones

1) Antidiuretic hormone (ADH) or vasopressin2) Oxytocin

Vasopressin and oxytocin, each has a characteristic binding polypeptide called neurophysin associated with it, in the granules of the neurons that secrete them. These are thought to be:

Neurophysin I carries oxytocin andNeurophysin II carries vasopressin.

When nerve impulses are transmitted downward along the fibers, the hormone is released from the secretory granules by Ca-dependant exocytosis and is absorbed into adjacent capillaries.

As hormone is loosely bound to neurophysin, it immediately separates while neurophysin has no known functions afterwards.

VASOPRESSIN RECEPTORS VIA, VIB and V2. All are G protein-coupled. The VIA and VIB act through phosphotidylinositol hydrolysis to increase the intracellular Ca conc.

The V2 act through c-AMP formation.

LocationLocation

VV22 ---- in the luminal ---- in the luminal membranes of renal collecting membranes of renal collecting

duct systemduct system

VVIAIA---- in the vascular smooth ---- in the vascular smooth muscle, liver and brainmuscle, liver and brain

Action of ADHAction of ADH

ADH has 2 main effects:

1. water re-absorption (retention) by distal tubules & collecting ducts of the kidneys.

* This effect is regulated by V2 receptors, through the

action of cAMP.

2. Contraction of vascular smooth muscles generalized vasoconstriction.

* This effect is regulated by V1 receptors, through the action

of IP3/Ca2+.

PHYSIOLOGIC FUNCTIONS OF ADHPHYSIOLOGIC FUNCTIONS OF ADH

Principal effect is retention of water by Principal effect is retention of water by the kidney, hence, often called the kidney, hence, often called AntidiureticAntidiuretic hormone (ADH)hormone (ADH) . .

It greatly increases the permeability of It greatly increases the permeability of the collecting ducts & collecting tubules the collecting ducts & collecting tubules to water and allows it’s reabsorption. In to water and allows it’s reabsorption. In

this way it conserves water and this way it conserves water and produces a very conc. urine. In the produces a very conc. urine. In the

absence of ADH , the tubules are absence of ADH , the tubules are impermeable to water and cause impermeable to water and cause

extreme dilution of urineextreme dilution of urine..

Figure 26.15a, b

The Effects of ADH on the distal collecting tubules and Collecting

Ducts

Mechanism of antidiuresisMechanism of antidiuresis

When ADH acts, it combines with When ADH acts, it combines with membrane receptors that form c-membrane receptors that form c-AMP. It phosphorylates the protein AMP. It phosphorylates the protein

channelschannels aquaporins aquaporins and insert and insert them in the apical portions of cells, them in the apical portions of cells,

thus providing high water thus providing high water permeabilitypermeability..

Formation of Water Pores: Mechanism of Vasopressin Action

Formation of Water Pores: Mechanism of Vasopressin Action

Facultative water reabsorption

All this occurs in 5 to 10 minutes. All this occurs in 5 to 10 minutes. Movement of water is by Movement of water is by simple simple

diffusiondiffusion. At least . At least 5 types5 types of of aquaporins have been identifiedaquaporins have been identified . .

1,21,2& & 33 are found in the kidneysare found in the kidneys , ,

44 is found in the brain andis found in the brain and

55 is found in the salivary and is found in the salivary and lacrimal glands and in the resp. lacrimal glands and in the resp.

tracttract..

REGULATION OF ADHREGULATION OF ADH Near the hypothalamus are modified Near the hypothalamus are modified

neuron receptors called neuron receptors called osmoreceptorsosmoreceptors. . When the ECF When the ECF

becomes too conc., fluid is pulled by becomes too conc., fluid is pulled by osmosis out of the osmoreceptor cell osmosis out of the osmoreceptor cell

decreasing it’s size and sending decreasing it’s size and sending signal to the hypothalamus to signal to the hypothalamus to

secrete ADH. Vice versasecrete ADH. Vice versa..

A second neuronal area important in A second neuronal area important in controlling osmolarity and ADH secretion is controlling osmolarity and ADH secretion is

located along the anteroventral region of the located along the anteroventral region of the third ventricle, called the third ventricle, called the AV3V regionAV3V region..

At the upper part of this region is a structure At the upper part of this region is a structure called the subfornical organ, and at the inferior called the subfornical organ, and at the inferior

part is another structure called the organum part is another structure called the organum vasculosum of the lamina terminalis vasculosum of the lamina terminalis (OVLT)(OVLT) . .

Between these two organs is the Between these two organs is the median median preoptic nucleuspreoptic nucleus, which has multiple nerve , which has multiple nerve connections with the two organs as well as connections with the two organs as well as

with the supraoptic nuclei and the blood with the supraoptic nuclei and the blood pressure control centers in the medulla of the pressure control centers in the medulla of the

brainbrain..

Control of ADH releaseControl of ADH release

1. Increased plasma osmolality, arterial blood pressure, due to blood volume ADH.

2. Age: ADH secretion water retention & hyponatremia.

3. Pain, nausea, emotional stress & physical trauma ADH secretion.

4. Drugs, e.g. morphine, barbiturates, & nicotine ADH

secretion.5. Alcohol ADH secretion.6. Hypoxia increases ADH secretion

http://www2.kumc.edu/ki/physiology/course/six/6_1.htmDr. Bolliger Kanas University Medical Center 1999

Vasoconstrictor effect of ADHVasoconstrictor effect of ADH

Higher conc. of ADH have a potent Higher conc. of ADH have a potent effect of constricting the arterioles , effect of constricting the arterioles , thus increasing the blood pressure. thus increasing the blood pressure.

For this reason ADH is also called For this reason ADH is also called VasopressinVasopressin..

Decreased blood volume esp. up to Decreased blood volume esp. up to 15-20%, strongly stimulates 15-20%, strongly stimulates

ADH secretion, the secretory rate ADH secretion, the secretory rate may rise to as high as 50 times may rise to as high as 50 times

normalnormal..

Mechanism of vasoconstrictionMechanism of vasoconstriction

The atria, esp. right atrium, have The atria, esp. right atrium, have stretch receptors which are stretch receptors which are

stimulated by overfilling. When they stimulated by overfilling. When they are excited, they send signals to are excited, they send signals to

brain to inhibit ADH secretionbrain to inhibit ADH secretion . .

Conversely when unexcited due to Conversely when unexcited due to under filling, greatly increased under filling, greatly increased

secretion of ADH occurssecretion of ADH occurs . .

Decreased stretch of Decreased stretch of baroreceptors of the carotid, baroreceptors of the carotid,

aortic and pulmonary regions aortic and pulmonary regions participate in increased ADH participate in increased ADH

secretionsecretion..

Control of ADH releaseControl of ADH release

1. in plasma osmolality, as in dehydration which will stimulate osmoreceptors in the hypothalamus ADH.

Hyperosmolarity of ECF

Receptors in hypothalam

us

More ADH release

Thirst

Collecting ducts of kidneys

Reabsorption of water

Water intake

Dilution of ECF

-ve feedback

Control of ADH release … cont.Control of ADH release … cont.

Loss of ECF volume

Less pressure in Rt. atrium & great

vessels

Less nerve impulse to the

hypothalamus

Thirst

More ADH release

More water reabsorption by kidneys

Water intake

Maintains ECF volume

2. blood volume ( 10%) stimulate mechanoreceptors in the great arteries (aorta & carotids) & right atrium ADH.

Abnormalities of ADH release – Abnormalities of ADH release – Hyposecretion:Hyposecretion:

Lack of ADH Diabetes insipidus.

2 types of DI: a. Neurogenic (central, or cranial) … Problem in Hypothalamus or Post

pituitary gland. b. Nephrogenic …resistance of V2

receptors in collecting ducts of the kidneys. - No ADH is needed as treatment.

Symptoms: Polyuria 20 L/day (N 1.5 L/d) specific gravity of urine (diluted urine),

plasma osmolality.

Primary Primary PolydypsiaPolydypsia

Patient drinks too much Patient drinks too much water that continuously water that continuously suppresses ADHsuppresses ADH

What happens if we give ADHWhat happens if we give ADH ? ?

DisorderDisorder AQP2 expression

Urine Urine osmolalityosmolality

Urine Urine volumevolume

Central Central Diabetes Diabetes InsipidusInsipidus

YesYes Will increaseWill increase Will Will decreasedecrease

Nephrogenic Diabetes Insipidus

NoNo No responseNo response No No changechange

Primary Primary PolydypsiaPolydypsia

Have to stop Have to stop patient from patient from drinking- the drinking- the ADH would ADH would increase on its increase on its ownown

Abnormalities of ADH release – Abnormalities of ADH release – Hypersecretion:Hypersecretion:

ADH, ‘Schwartz-Bartter Syndrome’: - occurs after surgery. - adenoma. - Bronchial carcinoma.

Signs & Symptoms:

- Hyponatremia - Mental confusion. - Coma.

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