Posterior pituitary peptide hormones

Antidiuretic hormone is a posterior pituitary peptide hormone that binds to vasoconstrictive Via receptors (via Gaq to activate PLC and thence increase cytsosolic Ca2+), to V2 receptors (causing kidney water reabsorption via Gas and increased cAMP) and to corticotropin secretion-regulating Vlb (V3) receptors (mediated by Gaq to activate PLC and thence increase cytosolic Ca2+). For bioactive-G protein interactions see Table 5.9. 

The posterior lobe of the pituitary, ie, the neurohypophysis, is under direct nervous control (1), unlike most other endocrine organs. The hormones stored in this gland are formed in hypothalamic nerve cells but pass through nerve stalks into the posterior pituitary. As early as 1895 it was found that pituitrin [50-57-7] an extract of the posterior lobe, raises blood pressure when injected (2), and that Pitocin [50-56-6] (Parke-Davis) causes contractions of smooth muscle, especially in the utems (3). Isolation of the active materials involved in these extracts is the result of work from several laboratories. Several highly active posterior pituitary extracts have been discovered (4), and it has been deterrnined that their biological activities result from peptide hormones, ie, low molecular weight substances not covalendy linked to proteins (qv) (5). 

The principal hormones of the human posterior pituitary include the two nonapeptides, oxytocin [50-56-6] and arginine vasopressin [11000-17-2] (antidiuretic hormone, ADH). Many other hormones, including opioid peptides (see Opioids, endogenous), cholecystokinin [9011-97-6] (CCK) (see Hormones, BRAIN oligopeptides), and gastrointestinal peptides, also have been located in mammalian neurohypophysis (6), but are usually found in much lower concentrations (7). Studies have demonstrated that oxytocin and vasopressin are synthesized in other human organs, both centrally and peripherally, and there is considerable evidence for their role as neurotransmitters (see Neuroregulators) (8). 

Vasopressin is a peptide hormone produced by the hypothalamus and secreted by the posterior pituitary in response to stimulation. Normal stimuli for vasopressin release are hyperosmolarity and hypovolemia, with thresholds for secretion of greater than 280 mOsm/kg and greater than 20% plasma volume depletion. A number of other stimuli, such as pain, nausea, epinephrine, and numerous drugs, induce release of vasopressin. Vasopressin release is inhibited by volume expansion, ethanol, and norepinephrine. The physiological effect of vasopressin is to promote free water clearence by altering the permeability of the renal collecting duct to water. In addition, it has a direct vasoconstrictor effect. Consequently, vasopressin results in water retention and volume restoration. In patients with septic shock, vasopressin is appropriately secreted in response to hypovolemia and to elevated serum osmolarity (R14). 

In heterodetic peptides, the ring system is formed from amides and other heteroatom linkages, for example, a disulfide bridge, a thioether or a lactone linkage. The most common nonamide links in heterodetic peptides are the disulfide bonds (found in posterior pituitary hormones such as oxytocin and vasopressin) and the ester (lactone) fnnction. " ... 

Oxytocin is a peptide hormone secreted by the posterior pituitary that participates in labor and delivery and elicits milk ejection in lactating women. During the second half of pregnancy, uterine smooth muscle shows an increase in the expression of oxytocin receptors and becomes increasingly sensitive to the stimulant action of endogenous oxytocin. Pharmacologic concentrations of oxytocin powerfully stimulate uterine contraction. 

Vasopressin is a peptide hormone released by the posterior pituitary in response to rising plasma tonicity or falling blood... 

Many small peptides exert their effects at very low concentrations. For example, a number of vertebrate hormones (Chapter 23) are small peptides. These include oxytocin (nine amino acid residues), which is secreted by the posterior pituitary and stimulates uterine contractions bradykinin (nine residues), which inhibits inflammation of tissues and thyrotropin-releasing factor (three residues), which is formed in the hypothalamus and stimulates the release of another hormone, thyrotropin, from the anterior pituitary gland. Some extremely toxic mushroom poisons, such as amanitin, are also small peptides, as are many antibiotics. 

Figure 30-1 (A) Median sagittal section of the human brain. From Maya Pines.15 (B) Drawing illustrating the synthesis of peptide hormones in the hypothalamus and transport via portal blood vessels into the anterior lobe of the pituitary gland or via nerve tracts into the posterior lobe.16...

Vasopressin and oxytocin are peptide hormones secreted from the posterior lobe of the pituitary gland. They function primarily to raise blood pressure (vasopressin), as antidiuretic (vasopressin), and to promote contraction of uterus and lactation muscies (oxytocin). The isolation, identification, and synthesis of these hormones was accomplished by Vincent du Vigneaud, for which he was awarded the Nobel Prize in chemistry in 1955. 

Vasopressin is a peptide hormone released by the posterior pituitary in response to rising plasma tonicity or falling blood pressure. Vasopressin possesses antidiuretic and vasopressor properties. A deficiency of this hormone results in diabetes insipidus (see Chapters 15 and 17). 

Specific dissection is performed on the brain and pituitary gland. Hypothalamic fragments may be dissected and shock frozen immediately in liquid nitrogen, for later extraction and determination of hypothalamic peptides. The pituitary gland is dissected, the posterior pituitary is stored separately, and the anterior pituitary is halved by a median-sagittal cut to obtain separate tissue samples for histology (fixation), and for subsequent analysis of hormone contents (stored frozen at -20 °C until hormone assay). 

Q3 Vasopressin is a small peptide hormone consisting of nine amino acids, most of which is synthesized in neurosecretory cells of the supraoptic nucleus of the hypothalamus. Small quantities are also produced in the neighbouring paraventricular nucleus. The hormone is transported down the axons of the neurosecretory cells via the infundibulum to the posterior pituitary, where it is stored until release into the blood is triggered by nerve impulses from the hypothalamus. Vasopressin is better known as antidiuretic hormone (ADH). The name vasopressin relates to its vasoconstrictor action, which increases pressure in the vascular system. This action was discovered before its effects on water retention were known. 

Q9 The hormone that contracts the uterus during labour is the peptide hormone oxytocin, which is released from the posterior pituitary gland. 

Anti-diuretic hormone (arginine vasopressin) is a nine-amino-acid peptide secreted from the posterior pituitary. Within hypothalamic neurons, the hormone is packaged in secretory vesicles together with a carrier protein called neurophysin both are released upon secretion. 

The most valuable confirmation of this view to date is, without doubt, to be found in the known structures of homologous proteins and peptide hormones, that is compounds of identical biological function isolated from different species. As is well known, the primary structures of the homologous insulins, corticotropins, hypertensins, posterior pituitary hormones, and heme peptide sequences from cytochromes c are closely similar and differ only at certain definite sites in the peptide chains. These can, in particular, serve as a useful point of departure in a search for more general principles governing protein structure, and in the comparison of different proteins. 

Oxytocin is a peptide hormone of the posterior pituitary gland. It stimulates the contractions of the pregnant uterus, which becomes much more sensitive to it at term. Patients with posterior pituitary disease (diabetes insipidus) can, however, go into labour normally. 

Peptides have been studied chiefly as a step toward the understanding of the much more complicated substances, the proteins. However, peptides are extremely important compounds in their own right the tripeptide glutathione, for example, is found in most living cells the nonapeptide oxytocin is a posterior pituitary hormone concerned with contraction of the uterus a corticotropin, made up of 39 amino acid residues, is one component of the adrenocorticotropic hormone ACTH. 

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