Hypothalamic -

Posterior pituitary axis

DR. ISAM ELDIN MOHAMED ABD ALLA
 Objectives:
By the end of the lecture the student should be
able to:
1. Describe hypothalamic- pituitary axis.
2. List steps of oxytocin & ADH synthesis.
3. Outline the mechanism of action &
physiologic effects of oxytocin &
vasopressin.
4. Outline regulation of oxytocin &
vasopressin secretion.
5. List & discuss pathophysiology of diabetes
insipidus & SIHADH
Hypothalamus:
-The portion of
anterior end of
diencephalon.
-Divided into nuclei
& nuclear areas.
- Connected to the
anterior pituitary via
portal vessels & to
posterior pituitary
by neural tract
Hypothalamic- Posterior pituitary Axis
Posterior pituitary lobe
(neurohypophysis): Is a
collection of endings of
axons arising from cell
bodies in supraoptic &
paraventricular nuclei i.e
has a neural connection to
the hypothalamus via
Hypothalamo-hypophysial
tract
Vasopressin & Oxytocin:-
Ø Are nonapeptide hormones synthesized in
cell bodies of neurons in supraoptic &
paraventricular nuclei.
ØTransported by Hypothalamo-hypophysial
tract to the posterior pituitary (stored) &
then secreted into the circulation.
Synthesis of ADH & Oxytocin:
§The precursor for these hormones are:
ØPreprooxyphysin = Signal peptide +
Oxytocin + Neurophysin-I.
produced mainly in paraventricular nuclei.

ØPrepropressophysin = Signal peptide +

Vasopressin+ neurophysin-II+ glycopeptide
Produced mainly via supraoptic nuclei
Vasopressin (Antidiuretic hormone ADH):
Acts by binding to G-protein coupled
surface membrane receptors of 3 types:
ØVIA, VIB (V3) receptors coupled via a G-
protein to phospholipase C → ↑second
messenger IP3 , DAG → intracellular Ca+2
ØV2 receptors coupled via Gs-protein to
adenylyl cyclase → ↑intracellular cyclic
AMP.
Physiologic effects of
vasopressin (ADH):-

1) The main physiologic

effect is stimulation of
water reabsorption
(Antidiuresis) via V2
receptors on renal
principal cells in distal
segment (late DT& CD).
Water retention maintain
plasma volume &
osmolality.
ØStimulate arteriolar vasoconstriction:
oTogether with angiotensin-11 vasopressin
constrict the arterioles via VIA receptors
reducing the vascular capacity (increasing
the peripheral resistance) to maintain BP in
case of acute loss of plasma volume as in
haemorrhage & other cause of ECF loss.
Regulation of ADH secretion:
Main stimulators for ADH secretion:
1. Plasma hyperosmolality.
2. Hypovolaemia (decreased ECF volume
by haemorrhage, diarrhoea, burn,
sweating, vomiting…. ).
3. Angiotensin-11
Other stimulators: pain, nausea,
hypoglycemia, & various drugs (nicotine,
opiates, antineoplastic agents)
Inhibitors of ADH secretion:
1. Plasma hypoosmolality.
2. Hypervolaemia (↑ed ECF volume) even
in presence plasma hyperosmolarity (via
inhibition of renin secretion inhibits both
ADH & aldosterone)
3. Alcohol (Ethanol).
4. ANP
 Diabetes insipidus DI:
A clinical condition of defective renal water
reabsorption.
Causes:
1. Vasopressin deficiency (Neurogenic,
central DI)
2. Unresponsive of renal principal cells to
ADH (nephrogenic DI) due to a defect in
the V2 receptor, Gs protein, adenylyl
cyclase or water channels aquapoein-2
DI is characterized by:
Ø Polyuria (excessive urination, urine
volume up to 23 liters/day) body fluids
become concentrated increased serum
osmolarity & Na+ concentration).
Ø Polydipsia (excessive thirst & water
drinking).
Case description:
A 56-year-old man with oat cell carcinoma of
the lung lung is admitted to the hospital after
having a grand mal seizure.
Laboratory findings:-
-plasma [Na+]: 110 mEq/L.
- plasma osmolarity: 225 mOsm/L
-Urine osmolarity: 650 mOsm/L
Q. comment on plasma [Na+] & osmolality?
Q what is the cause of grand mal seizure?
Q what is the pathophysiology& diagnosis?
Syndrome of inappropriate
hypersecretion of ADH (SIADH):
§Excess ADH secretion via lung tumor →
renal water reabsorption inappropriate to
ECF osmolality→ dilution of body fluids
while concentrating the urine.
Treatment:
ØADH antagonist (demeclocycline) or
ØWater restriction.
Physiologic effects of Oxytocin:
§Acts via G- protein coupled receptor that ↑ the
intracellular Ca+2 to exert these effects:
1) Contraction of pregnant uterus during labor),
this action is synergized by oestrogens &
antagonized by progesterone.
Oestrogens ↑ excitability of the uterus, number
of oxytocin receptors, gap junctions between
myometrial cells & prostaglandins production.
Oxytocin stimulates local production of
prostaglandins which reinforce the contraction.
reflex:
Stimulation of touch receptors around breast
nipple during suckling→ Sensory impulses to
the hypothalamus→oxytocin secretion →
contraction of myoepithelial cells around the
milk sinuses → milk ejection
Regulation of Oxytocin secretion:
§Oxytocin is secreted in response to:
Ø Touch of the dilated uterine cervix by foetal
head during labor .
Ø Touch of breast nipple by infant`s mouth
during suckling.
ØGenital stimulation & emotional stimuli
(sight, sound & smell of infant) in lactating
mothers.
Ø Stress.
§Oxytocin secretion is inhibited by alcohol &
opiates .