Hormones of the neurohypophysis

Antidiuretic hormone (ADH), also referred to as vasopressin, has two major effects, both of which are reflected by its names (1) antidiuresis (decrease in urine formation by the kidney) and (2) vasoconstriction of arterioles. 

Antidiuretic hormone promotes the reabsorption of water from the tubules of the kidney, or antidiuresis. Specifically, it acts on the collecting ducts and increases the number of water channels, which increases the diffusion coefficient for water. This results in the body s conservation of water and the production of a low volume of concentrated urine. The reabsorbed water affects plasma osmolarity and blood volume. This effect of ADH on the kidney occurs at relatively low concentrations. At higher concentrations, ADH causes constriction of arterioles, which serves to increase blood pressure. Antidiuretic hormone secretion is regulated by several factors  

The primary factor that influences ADH secretion is a change in plasma osmolarity. Osmoreceptors in the hypothalamus are located in close proximity to the ADH-producing neurosecretory cells. Stimulation of these osmoreceptors by an increase in plasma osmolarity results in stimulation of the neurosecretory cells an increase in the frequency of action potentials in these cells and the release of ADH from their axon terminals in the neurohypo- 

Hypothalamic osmoreceptors have a threshold of 280 mOsM. Below this value, they are not stimulated and little or no ADH is secreted. Maximal ADH levels occur when plasma osmolarity is about 295 mOsM. Within this range, the regulatory system is very sensitive, with measurable increases in ADH secretion occurring in response to a 1% change in plasma osmolarity. Regulation of ADH secretion is an important mechanism by which a normal plasma osmolarity of 290 mOsM is maintained. 

Other factors regulating ADH secretion include blood volume and blood pressure. A decrease in blood volume of 10% or more causes an increase in ADH secretion sufficient to cause vasoconstriction as well as antidiuresis. A decrease in mean arterial blood pressure of 5% or more also causes an increase in ADH secretion. The resulting water conservation and vasoconstriction help increase 

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At Hofmann-La Roche the work of K. Vogler and R.O. Studer on cyclic peptide antibiotics, for instance the polymyxins, is particularly noteworthy. At SANDOZ, R.A. Boissonnas was the primary mover of peptide studies. His work on mixed anhydrides (cf. p. 81) was the starting point of a continued research effort in which S. Guttmann, J. Pless. E. Sandrin, R. Huguenin, P.A. Jaquenoud, H. Bossert, W. Bauer and several younger associates participated. After early syntheses of the hormones of the neurohypophysis they became leaders in the synthesis of biologically active peptides on an industrial scale and first made oxytocin, then more complex molecules such as salmon calcitonin or more recently a cychc peptide with somatostatin activity, commercially available. 

Corticotropin-Releasing Factor. A hormone-like factor found recently in the midbrain affects the adenohypophysis. This factor, like the hormones of the hypophyseal posterior lobe, is a neurosecretion. Progress has been made in its enrichment it may be related to the hormones of the neurohypophysis. It is not yet clear whether this factor is a link in the chain of the self-regulation of the hypophysis-adrenal cortex system, or whether it merely releases the stress reaction. 

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). 

List functions and describe mechanisms regulating release of hormones from the neurohypophysis... 

As discussed previously, the neurohypophysis has a direct anatomical connection to the hypothalamus. Therefore, the hypothalamus regulates the release of hormones from the neurohypophysis by way of neuronal signals. Action potentials generated by the neurosecretory cells originating in the hypothalamus are transmitted down the neuronal axons to the nerve terminals in the neurohypophysis and stimulate the release of the hormones into the blood. The tracts formed by these axons are referred to as hypothalamic-hypophyseal tracts (see Figure 10.2). The action potentials are initiated by various forms of sensory input to the hypothalamus. Specific forms of sensory input that regulate the release of ADH and oxytocin are described in subsequent sections in this chapter. 

Morphine causes oliguria, which results from (1) pronounced diaphoresis, (2) the relative hypotension and decreased glomerular filtration rate, and (3) the release of antidiuretic hormone from the neurohypophysis. In an elderly patient with prostatic hypertrophy, morphine may cause acute... 

In the course of the isolation of oxytocin, the second principal hormone of the pituitary gland, vasopressin, a peptide with pressor and antidiuretic effects, was similarly secured in pure form. Porcine glands yielded a vasopressin that contained lysine, while an arginine containing peptide was obtained from the neurohypophysis of cattle. Structure elucidation [63,64] revealed that the two vasopressins are quite analogous to oxytocin, except that isoleucin in position 3 of oxytocin is replaced by phenylalanine and position 8 is occupied by one of the basic amino acids, lysine or arginine, rather than by leucine ... 

The role of the pituicyte in the secretory mechanism of the antidiuretic hormone remains unsettled. This cell could act as a storage site for the active polypeptides, which would then be released from the cells of the posterior lobe into the bloodstream as needed. The posterior lobe is more sensitive to changes in the water content of blood because it is not separated from circulating blood by the blood-brain barrier. That the pituicytes affect polypeptide hormone secretion is suggested by the fact that continued stimulation of the neurohypophysis causes the mitotic rate in pituicytes to increase. 

BERDE B., BOISSONNAS R.A. Basic pharmacological properties of synthetic analogues and homologues of the neurohypophysial hormones. In Netirohypophysial Hormones and Similar Polypeptides (B.BERDE, ed.),... 

Metabolic activation may be a feature in the biosynthesis of the neurohypophysial hormones (15) but there is no evidence for... 

The ultrastructure of the neurohypophysis has been described in such detail to provide a background for a discussion of the mechanism of release of the hormone. Several anatomists seem to agree that it is little likely that secretion occurs by a reverse pinocytosis. If the granules are not released to the blood, one would have to explain what becomes of the granule membrane after hormone has left it. The rate of turnover of granules in the neural lobe is unknown. Several possibilities seem to exist for a... 

Stimulation and inhibition of thyroid-stimulating hormone (TSH) release by neurohypophysial hormones have been reported. Stimulation of growth hormone release by Lys -vasopressin has been demonstrated in the primates but not in other species. There is indirect evidence for the functional role of the neurohypophysial hormones in gonadotrophine secretion. The role of oxytocin in prolactin secretion is not clear. 

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). 

AVP plays a central role in water homeostasis of terrestrial mammals, leading to water conservation by the kidney. OT is primarily involved in milk ejection, parturition and in sexual and maternal behaviour. Both hormones are pqDtides secreted by the neurohypophysis, and both act also as neurotransmitters in the central nervous system (CNS). The major hormonal targets for AVP are the renal tubules and vascular myocytes. The hormonal targets for OT are the myoepithelial cells... 

As its name implies, the neurohypophysis is derived embryonically from nervous tissue. It is essentially an outgrowth of the hypothalamus and is composed of bundles of axons, or neural tracts, of neurosecretory cells originating in two hypothalamic nuclei. These neurons are referred to as neurosecretory cells because they generate action potentials as well as synthesize hormones. The cell bodies of the neurosecretory cells in the supraoptic nuclei produce primarily antidiuretic hormone (ADH) and the cell bodies of the paraventricular nuclei produce primarily oxytocin. These hormones are then transported down the axons to the neurohypophysis and stored in membrane-bound vesicles in the neuron terminals. Much like neurotransmitters, the hormones are released in response to the arrival of action potentials at the neuron terminal. 

The adenohypophysis is derived embryonically from glandular tissue, specifically, Rathke s pouch. This tissue originates from the oropharynx, or the roof of the mouth. It then migrates toward the embryonic nervous tissue destined to form the neurohypophysis. When these two tissues come into contact, Rathke s pouch loses its connection with the roof of the mouth and the pituitary gland is formed. Unlike the neurohypophysis, which releases hormones originally synthesized in the hypothalamus, the adenohypophysis synthesizes its own hormones in specialized groups of cells. Similar to the neurohypophysis, however, the release of these hormones into the blood is regulated by the hypothalamus. 

Vasopressin (antidiuretic hormone) is a peptide synthesized in the hypothalamus and secreted from the neurohypophysis of the pituitary gland. This substance plays an important role in the long-term regulation of blood pressure through its action on the kidney to increase reabsorption of water. The major stimulus for release of vasopressin is an increase in plasma osmolarity. The resulting reabsorption of water dilutes the plasma toward its normal value of 290 mOsM. This activity is discussed in more detail in Chapter 10 (the endocrine system) and Chapter 19 (the renal system). 

In order to make adjustments in the water load, the reabsorption of the remaining 20% of the filtered water from the distal tubule and the collecting duct is physiologically controlled by antidiuretic hormone (ADH), also referred to as vasopressin. Antidiuretic hormone, synthesized in the hypothalamus and released from the neurohypophysis of the pituitary gland, promotes the... 

The axonal processes of hypothalamic neurons project to the neurohypophysis, where they store the nona-peptides vasopressin (= ancidiuretic hormone, ADH) and oxytocin and release them on demand into the blood. Therapeutically (ADH, p. 64, oxytocin, p. 126), these peptide hormones are given pa-renterally or via the nasal mucosa... 

Historically vasopressin and oxytocin, two nonapep-tides, were the first peptide neurohormones to be considered they are stored in the neurohypophysis and released into the bloodstream upon an appropriate stimulus. In the periphery, oxytocin stimulates the contraction of epididymal and uterine smooth muscle (see Chapter 62) and vasopressin (antidiuretic hormone) facilitates the reabsorption of water from the kidney tubules. In addition to these well-accepted roles as neurohormones, there is convincing evidence that these compounds function as neurotransmitters they both possess potent inhibitory actions on neurohypophyseal neurons. The significance of their neurotransmitter function is not yet clear. 

Connected to the brain by a stalk (Fig. 30-1), the pituitary gland releases at least ten peptide or protein hormones that regulate the activity of other endocrine (hormone-producing) glands in distant parts of the body. The pituitary is composed of several distinct parts the anterior lobe (adenohypophysis), a thin intermediate portion (pars intermedia), and a posterior lobe (neurohypophysis). Each has its own characteristic endocrine functions. 

Shaw FD, Dyball REJ, Nordmann JJ (1983) Mechanisms of inactivation of neurohypophysial hormone release, In Cross BA, Leng G (Eds), The Neurohypophysis Structure, Function and Control, Progress in Brain Reseach, Vol. 60, pp. 305-317. Elsevier, Amsterdam. 

Antidiuretic hormone (ADH) In cirrhotic and ascitic patients, the ADH level is usually elevated, (s. tab. 16.5) With a reduced effective plasma volume, ADH is released by non-osmotic stimulation in the neurohypophysis and possibly broken down in the liver at a reduced rate as well. The plasma activity of ADH largely... 

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