chemistry and mechanism of action

1. OXYTOCIN AND
VASOPRESSIN
KEERTHANA. M
II M.Sc
BIOCHEMISTRY

2. OXYTOCIN
 Source of Secretion:
◦ Secreted mainly by paraventricular nucleus
and partly supraoptic nuclei.
◦ Transported from hypothalamus to posterior
pituitary through the nerve fibers of
hypothalamo-hypophyseal tract.
◦ In the posterior pituitary, the oxytocin is
stored in the nerve endings of hypothalamo-
hypophyseal tract.
◦ When suitable stimuli reach the posterior
pituitary from hypothalamus, oxytocin is
released into the blood.
◦ Oxytocin is secreted in both males and
females.

3. OXYTOCIN
 Chemistry and half – life
 Oxytocin is a polypeptide containing 9
aminoacids.
 It has a half-life of about 6 minutes

4.  Action:
 Action on mammary glands (milk
letdown/ milk ejection reflex)
 Action on uterus

5. Action on mammary glands
◦ Causes ejection of milk from the
mammary glands.
◦ Oxytocin causes contraction of the
myoepithelial cells and flow of milk from
alveoli of mammary glands to the exterior
through duct system and nipple.
◦ The process by which the milk is ejected
from alveoli of mammary glands is called
milk ejection reflex or milk letdown
reflex.
◦ It is one of the neuro-endocrine
reflexes.

6. Milk ejection reflex

7. Action on mammary glands
◦ As this reflex is initiated by the nervous
factors and completed by the hormonal
action, it is called a neuroendocrine
reflex.
◦ During this reflex, large amount of
oxytocin is released by positive
feedback mechanism

9. Action on uterus
• Oxytocin acts on:
 Pregnant uterus
 Non-pregnant uterus

10. Action on pregnant uterus
◦ Throughout the period of pregnancy, oxytocin
secretion is inhibited by estrogen and
progesterone.
◦ At the end of pregnancy, the secretion of these
two hormones decreases suddenly and the
secretion of oxytocin increases.
◦ Oxytocin causes contraction of uterus and helps
in the expulsion of fetus.
◦ It is also an example of neuro-endocrine reflex
and positive feedback mechanism

11. On pregnant uterus

12. On pregnant uterus

13. Action on non-pregnant
uterus
 Action of oxytocin on non-pregnant
uterus is to facilitate the transport of
sperms through female genital tract up
to the fallopian tube, by producing the
uterine contraction during sexual
intercourse

14. On non-pregnant uterus

15. Vasopressin
 Also called as anti diuretic hormone
 Source of Secretion
◦ Secreted mainly by supraoptic and
paraventricular nucleus in small quantity.
◦ From here, this hormone is transported to
posterior pituitary through the nerve fibers
of hypothalamo-hypophyseal tract, by
means of axonic flow.

16.  Chemistry and Half-life
◦ Polypeptide containing 9 amino acids.
◦ Its half-life is 18 to 20 minutes

17. Actions
◦ Antidiuretic hormone has two actions:
 Retention of water
 Vasopressor action

18. Retention of water
◦ Major function of ADH is retention of water
by acting on kidneys.
◦ It increases the facultative reabsorption
of water from distal convoluted tubule and
collecting duct in the kidneys.

19.  Mode of action on renal tubules
1.Without ADH, the luminal membranes of
the tubular epithelial cells of the
collecting ducts are almost impermeable
to water.
2.Immediately inside the cell membrane
are a large number of special vesicles
that have highly water permeable pores
called aquaporins.
3.When ADH acts on the cell, it first
combines with membrane receptors (V2
Receptors) that activate adenylyl
cyclase and cause the formation of
cAMP inside the tubular cell cytoplasm

20. 4.This causes phosphorylation of elements
in the special vesicles, which then
causes the vesicles to insert into the
apical cell membranes, thus providing
many areas of high water permeability.
5.All this occurs within 5 to 10 minutes.
6.Then, in the absence of ADH, the entire
process reverses in another 5 to 10
minutes.
7.Thus, this process temporarily provides
many new pores that allow free diffusion
of water from the tubular fluid through the
tubular epithelial cells and into the renal
interstitial fluid

21. Vasopressor action
◦ In large amount, ADH shows vasoconstrictor
action.
◦ Particularly, causes constriction of the
arteries in all parts of the body.
◦ Due to vasoconstriction, the blood pressure
increases.
◦ ADH acts on blood vessels through V1A
receptors.
◦ However, the amount of ADH required to
cause the vasopressor effect is greater than
the amount required to cause the
antidiuretic effect.

22. ◦ One of the stimuli for causing intense
ADH secretion is decreased blood
volume.
◦ This occurs especially strongly when the
blood volume decreases 15 to 25 per cent
or more; the secretory rate then
sometimes rises to as high as 50 times
normal.

23. Mode of action
1.The atria have stretch receptors that are
excited by overfilling.
2.When excited, they send signals to the
brain to inhibit ADH secretion.
3.Conversely, when the receptors are
unexcited as a result of underfilling, the
opposite occurs, with greatly increased
ADH secretion.
4.Decreased stretch of the baroreceptors
of the carotid, aortic, and pulmonary
regions also stimulates ADH secretion

25. Regulation of secretion
◦ ADH secretion depends upon the volume
of body fluid and the osmolarity of the
body fluids.
◦ Potent stimulants for ADH secretion are:
 Decrease in the extracellular fluid (ECF)
volume
 Increase in osmolar concentration in the
ECF.

27. Applied physiology
 Hypersecretion
 Syndrome of
Inappropriate
Hypersecretion of
Antidiuretic
Hormone (SIADH)
 Hyposecretion
 Diabetes insipidus

28. SIADH
 SIADH is the disease characterized by loss of
sodium through urine due to hypersecretion of
ADH
 Causes
◦ SIADH occurs due to cerebral tumors, lung
tumors and lung cancers because the tumor
cells and cancer cells secrete ADH.
◦ In normal conditions, ADH decreases the
urine output by facultative reabsorption of
water in distal convoluted tubule and the
collecting duct.
◦ Urine that is formed is concentrated with
sodium and other ions.

29. Signs and symptoms
1.Loss of appetite
2.Weight loss
3.Nausea and vomiting
4.Headache
5.Muscle weakness, spasm and cramps
6.Fatigue
7.Restlessness and irritability.
8.In severe conditions, the patients die
because of convulsions and coma.

30. Diabetes insipidus
 Diabetes insipidus is a posterior pituitary disorder
characterized by excess excretion of water through
urine due to a defect in ADH secretion
 Causes:
◦ This disorder develops due to the deficiency
of ADH, which occurs in the following
conditions:
 Lesion (injury) or degeneration of supraoptic and
paraventricular nuclei of hypothalamus
 Lesion in hypothalamo-hypophyseal tract
 Atrophy of posterior pituitary
 Inability of renal tubules to give response to ADH
hormone. (Nephrogenic diabetes insipidus)

31. Signs and symptoms
 Polyuria
 Polydipsia
 Dehydration

32. THANK YOU