Table of Contents
Oxytocin is synthesized in the paraventricular nuclei of the hypothalamus. Like most other hormones, the synthesis occurs as inactive precursor protein from which the successive hydrolysis leads to the release of the final active oxytocin.
Neurophysin 1 is characteristic precursor carrier protein which is present in the precursor state. It should be noted that the secretion does not occur at the place of synthesis. The transport of the synthesized hormone occurs to the posterior pituitary gland via the stalk.
The characteristic storage bodies of the oxytocin in the posterior pituitary are known as Herring bodies (which are present in the axon terminal is present in the posterior pituitary). The release of the oxytocin from the end of the posterior pituitary requires a depolarizing signal to the nerve terminal.
One of the characteristic proteins which is required during the hydrolysis of the oxytocin is the peptidylglycine alpha-amidating monooxygenase. This enzyme in turn requires vitamin C as the necessary cofactor. Oxytocin gets metabolized by means of enzyme known as oxytocinase.
Though the posterior pituitary forms the major neural source of the oxytocin, it should be noted that there are non-neural sources of oxytocin like the corpus luteum and placenta in the case of female and leydig cells in the case of males.
Function of oxytocin
Oxytocin is important in parturition as it stimulates uterine contractions and in breast feeding as it induces myoepithelial contractions. Oxytocin, which is usually released via the suckling reflex, stimulates the contraction of the smooth-muscle cells in the lactiferous ducts causing milk let down. Prolactin is responsible for the production of milk whereas the oxytocin is responsible for the milk ejection.
In both instances, there is a positive feedback loop involved in their release. Uterine contractions are prompted and further promoted by uterine stretch while breast myoepithelial contractions is promoted by the suckling action of the infant. The positive feedback loop is a characteristic feature of oxytocin as other endocrine hormones generally have a negative feedback loop. Ferguson reflex refers to the release of the oxytocin on the dilation of the cervical and vaginal region.
Oxytocin in Labour
Mechanism of action of oxytocin in uterus
The contraction of the uterus, which is produced by oxytocin, is the physiological uterine contraction and the law of priority is maintained (it should be known that the ergometrine causes complete loss of polarity during its contraction). The onset of action is also faster with oxytocin when compared to the ergometrine but it is short lived.
To the biochemical level, oxytocin acts through the G protein coupled receptor, which in turn acts via the phosphatidylinositol calcium channel. This in turn leads to the release of prostaglandins and leukotrienes. Oxytocin increases both the frequency as well as the force of contraction of uterus and only at higher doses causes prolonged and sustained contractions.
The duration of action of syntocinon is for 8 minutes. One more prime difference when compared to the ergometrine is that syntocinon is available only in the parenteral route, whereas the ergometrine is available both in oral formulation as well as in the parenteral route.
Clinically, oxytocin is used for the induction of labour and during the labour uterine contraction it helps in the augmentation. In the case of postpartum haemorrhage, it is used along with the ergometrine.
Therapeutic Uses of Oxytocin
Role of oxytocin in pregnancy
Oxytocin is used in the pregnancy to accelerate abortion especially in the case of missed abortions and also in the case of expulsion of the hydatidiform mole. It is also used for ripening of the cervix before induction of the labour and in the case of uterine inertia.
Role of oxytocin in males
The oxytocin receptors are found in the epididymis and in research it has been found to increase the motility of the sperm as well as the number of the sperm. It also helps in the conversion of dihydrotestosterone.
Diagnostic role of oxytocin
Oxytocin is used in the diagnostic tests contraction stress test and oxytocin sensitivity test, which are currently not routinely used.
Future therapeutic options
Oxytocin is researched as a major trust producing hormone and in a lighter note has been tried as a love making hormone, confidence generating hormone and used in relationship counselling.
In lactation deficiency, the nasal spray formulations of oxytocin have been tried.
Oxytocin nasal spray has been tested for a lot of social disorders in addition to depression. It is currently in the clinical trials for a variety of psychiatric disorders like schizophrenia and autism.
Side Effects and Contraindications of Oxytocin
The side effects of oxytocin are hyperstimulation of the uterus, water intoxication due to the antidiuretic effect (structural similarity with the vasopressin), rupture of the uterus, hypotension and pain of the anginal variety. All these will also have effect on the foetus, leading to fetal distress, hypoxia and even fetal death.
Available evidence shows that for the augmentation of a delayed labour, the high dose regimen of oxytocin will be reducing the length of the labour and also the number of cesarean sections. In addition, it also increases the vaginal birth which will occur spontaneously. Whereas in the case of induction of labour, the high dose and low dose have not shown any significant differences.
The contraindication for giving oxytocin include cephalopelvic disproportion, malposition of the foetus, hypertonic uterine pattern and any other contraindication for the vaginal delivery.
Atosiban on the other hand, an oxytocin receptor antagonist, can be used as a tocolytic in preterm labor. It is used as a tocolytic in the uncomplicated premature labour and it is available in Europe but not the United States. This is basically a second line of treatment after nifedipine (which is most commonly used for the preterm labour in between 32nd to 36th week). The efficacy of atosiban in a meta-analysis has been compared to that of beta agonists.
ADH is synthesized in the suprachiasmatic nuclei of the hypothalamus. It should be noted that the secretion does not occur at the place of synthesis. The transportation of the synthesised hormone occurs to the posterior pituitary gland via the stalk. When the impulse for the secretion arises, the secretion occurs from the posterior pituitary. At supra-physiologic levels, ADH acts on V1 receptors to cause vasoconstriction, hence the term vasopressin.
Function of vasopressin
The primary function of the vasopressin is to function in the retirement of the water in the body and the construction of the blood vessels. ADH release normally occurs following stimulation of osmoreceptors usually due increased plasma osmolality. ADH acts on V2 receptors at the distal kidney tubule and the collecting duct by causing insertion of aquaporin channels, thus increasing their permeability to water.
The resulting increased permeability of the collecting ducts causes reabsorption of water to occur as water enters the hypertonic interstitium of the renal pyramids, thus concentrating the urine. In the absence of ADH, the urine is hypotonic to plasma (dilute urine), urine volume is increased, and there is net water loss leading to increased osmolality of body fluids.
Other functions of vasopressin
- ADH also promotes the release of von Willebrand factor) and factor VIII from the endothelium.
- Though most of the vasopressin is released into the blood vessels from the posterior pituitary, some amount is released directly into the brain. This raises the question about the other important role of vasopressin in many other complex social behaviours and maternal responses (areas still to be explored).
- The vasoconstriction function of the vasopressin, though not of great significance in effect in normal health individuals, plays an important role in hemorrhage patients with shock. The compensation by means of vasoconstriction results in an increase in the pressure by means of increasing the peripheral vascular resistance.
- Vasopressin also plays an important role in the circadian rhythm. It also has its effect on the release of corticosteroids from the adrenal gland (along with the CRH).
The decrease in the secretion of the vasopressin or alteration in the effect of the vasopressin in the kidney result in a characteristic disease known as diabetes insipidus.
The increase in the secretion leads to hyponatremia and when it occurs as a result of hypovolemia it would lead to the hypovolemic hyponatremia. In addition to this, there exists euvolemic hyponatremia as well as hypervolemic hyponatremia, which occurs in the diseased state such as nephrotic syndrome and failure of the heart.
The inappropriate secretion of the SIADH in the case of euvolemic hyponatremia is known as syndrome of Inappropriate antidiuretic hormone secretion. The causes include most characteristic the small cell carcinoma of the lung and also due to a number of drug such as SSRI, tricyclic antidepressants.
Vasopressin as therapeutic drug
Pharmacologically, the vasopressin analogues are used in the management of von Willebrand Disease (vWD) type I and Hemophilia A. They are the second line of choice in shock patients after the failure of response to norepinephrine and dopamine.