Biological Chemistry - Berezov T. T., Korovkin B. F. 1998

Hormones
Pituitary Hormones
Vasopressin and Oxytocin

The Hormones Vasopressin and Oxytocin are synthesized ribosomally. Specifically, three Proteins—neurophysins I, II, and III—are synthesized simultaneously in the Hypothalamus. Their function is to non-covalently bind oxytocin and vasopressin and transport these hormones into the neurosecretory granules of the hypothalamus. Subsequently, as neurophysin-hormone complexes, they migrate along the axon to the posterior Pituitary Gland, where they are stored as a reserve; upon dissociation of the complex, the free hormone is secreted into the Blood. Neurophysins have also been isolated in pure form, and the Introduction/19.html">Primary Structure of two of them has been elucidated (consisting of 92 and 97 amino acid residues, respectively); these are Cysteine-rich proteins containing seven Disulfide Bonds each.

The Chemical Structure of both hormones was elucidated through the classic works of V. du Vigneaud and co-workers, who were the first to isolate these hormones from the posterior pituitary and accomplish their chemical synthesis. Both hormones are nonapeptides with the following structures:

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Vasopressin differs from oxytocin by Two Amino Acids: it contains phenylalanine instead of isoleucine at position 3 from the N-terminus, and Arginine instead of leucine at position 8. This sequence of 9 amino acids is characteristic of vasopressin in humans, monkeys, horses, cattle, sheep, and dogs. In the vasopressin molecule from the porcine pituitary gland, Lysine is present at position 8 instead of arginine, hence the name "lysine-vasopressin." In all vertebrates except mammals, vasotocin has additionally been identified. This hormone, which consists of the oxytocin ring with its S—S bridge and the vasopressin side chain, was chemically synthesized by V. du Vigneaud long before the natural hormone was isolated. It has been suggested that, evolutionarily, all neurohypophysial hormones originated from a single common precursor—namely, arginine-vasotocin—from which modified hormones evolved via single triplet Mutations in the genes.

The primary biological effect of oxytocin in mammals is associated with The stimulation of uterine smooth Muscle contraction during labor and the contraction of muscle fibers surrounding the alveoli of the Mammary Glands, which triggers milk secretion. Vasopressin stimulates the contraction of vascular smooth muscle fibers, exerting a strong vasopressor effect; however, its main physiological role is the Regulation of Water METABOLISM, hence its alternative name, antidiuretic hormone. In low concentrations (0.2 ng per 1 kg of body weight), vasopressin exerts a potent antidiuretic effect by stimulating the reabsorption of water across the membranes of the renal tubules. Under normal conditions, it controls the Osmotic Pressure of Blood Plasma and the body's water balance. In pathological conditions, particularly Atrophy of the posterior pituitary, diabetes insipidus develops—a disorder characterized by The excretion of extremely large volumes of urine, caused by a disruption in the water reabsorption process within the renal tubules.

Regarding the MECHANISM OF ACTION of neurohypophysial hormones, it is known that their hormonal effects, particularly those of vasopressin, are mediated via the adenylate cyclase system (see below). However, the exact mechanism by which vasopressin regulates water transport in the Kidneys remains unclear.