Hormones of the Posterior Pituitary Gland

HORMONES OF THE POSTERIOR PITUITARY GLAND

Antidiuretic hormone (ADH) and oxytocin are synthe-sized in the supraoptic and paraventricular nuclei in the brain and are transported in secretory granules through axons to the posterior lobe. These hormones are cyclic peptides of eight amino acids. Each is synthesized as a larger precursor, which is processed into the hormone plus a protein that binds the hormone, called neuro-physin. ADH and oxytocin have different amino acids at positions 3 and 8.

Antidiuretic Hormone

ADH (vasopressin) is released primarily in response to increases in plasma osmolarity or decreases in blood volume. It produces its antidiuretic activity in the kid-ney, causing the cortical and medullary parts of the col-lecting duct to become more permeable to water, thereby increasing water reabsorption, reducing serum osmolarity, and increasing its volume. It produces this effect by binding to a subset of vasopressin receptors (Table 59.3) called V₂ that have relatively high affinity for the hormone. ADH also has actions at sites other than the kidney. V₂ receptors also mediate an increase in circulating levels of two proteins involved in blood coagulation: factor VIII and von Willebrand’s factor. At higher concentrations, ADH interacts with V₁ receptors to cause a general constriction of most blood vessels. It also interacts with V₃ (or V_1b) receptors to increase ACTH release, although the major control of ACTH re-lease occurs through corticotropin-releasing hormone.

ADH itself is available for injections (Pitressin) but has a half-life of about 15 minutes. Desmopressin (DDAVP) is an analogue without an amino group at the first amino acid and with D-arginine instead of L-arginine. This analogue is more stable and has very little pressor activity. Desmopressin can be given subcuta-neously or nasally, and the effects last for 12 hours.

Because it is stable, desmopressin is preferred for treatments especially if pressor effects are not desired. The primary indication for therapy is central diabetes insipidus, a disorder that results when ADH secretion is reduced and that is characterized by polydipsia, polyuria, and dehydration. Desmopressin is also used to reduce primary nocturnal enuresis, or bedwetting, in children. It is useful in people with mild hemophilia A or with some types of von Willebrand’s disease, in which von Willebrand’s factor is present at low levels. In these cases, desmopressin is given when excessive bleeding occurs or before surgery to help reduce bleeding indi-rectly by increasing the amounts of coagulation factors.

A possible adverse effect of desmopressin is water in-toxication if too much is taken.

ADH antagonists, including nonpeptide analogues that may be taken orally, have been developed with specificity for each of the receptor types. In the future, those that block V₁ receptors may be useful in treating hypertension, and those that block V₂ receptors may be useful in any condition of excessive water retention or hyponatremia, for which so far there is no satisfactory therapeutic treatment.

Oxytocin

Oxytocin (Pitocin, Syntocinon) causes milk release (let-down) by stimulating contraction of the myoepithelial cells of the milk ducts in lactating mammary glands; this forces milk from the alveoli of the breast. Oxytocin re-lease is stimulated by suckling and by auditory and vi-sual stimuli, such as a baby’s cry. Oxytocin is available as a nasal spray, which is used as an aid to lactation when milk ejection is impaired.

Oxytocin also stimulates contraction of uterine smooth muscle in late phases of pregnancy.