Prolactin-inhibiting hormone, actions

A role for cyclic AMP as a mediator for the actions of prolactin has been proposed, but the bulk of the evidence available suggests that it is not directly involved. It is possible that levels of cyclic AMP-dependent protein kinase are limiting, rather than cyclic AMP itself, and that these can be increased by prolactin, presumably by induction of the appropriate genes [67]. Cyclic AMP derivatives do not mimic the actions of prolactin in in vitro systems. Indeed, they may inhibit some actions of the hormone, including stimulation of synthesis of milk proteins, fatty acids, DNA and RNA in mammary gland explants [79-81]. 

Pinilla L, Gonzalez LC, Tena-Sempere M, Aguilar E (2001) Evidence for an estrogenlike action of raloxifene upon the hypothalamic-pituitary unit raloxifene inhibits luteinizing hormone secretion and stimulates prolactin secretion in ovariectomized female rats. Neurosci Lett 311 149-152... 

Nickel ions have been shown to depress the in vivo and in vitro release of prolactin [336], while the release of growth hormone was stimulated, and only at relatively high ion concentrations. Hyperglycemia occurs in rats following intraperitoneal or intratracheal injections of NiCl2 [265, 337, 338], The mechanism of action of nickel appears to be inhibition of insulin release this inhibition could be related to the extremely high concentration of nickel found in the pituitary and the effect on the secretion of the pituitary hormones (growth hormone and adrenocorticotropic hormone). 

Rettori V, Wenger T, Snyder G, Dalterio S, McCann SM. (1988). Hypothalamic action ofdelta-9-tetrahydrocannabinol to inhibit the release of prolactin and growth hormone in the rat. Neuroendocrinology. 47(6) 498-503. 

FIGURE 8.4 The Bronson model of priming pheromone actions in rodents. Chemical signaling between males and females constitutes a feedback mechanism that results in accelerated maturation and reproduction. This, in turn, permits the mice to adjust their reproduction and population size quickly to respond to environmental conditions such as sudden food abundance at harvest time. FSH, follicle-stimulating hormone LH, luteinizing hormone PRL, prolactin. Stimulation and inhibition are marked by - - and —, respectively. (From Bronson and Coquelin, 1980.)... 

All antipsychotics except clozapine and perhaps olanzapine produce hyperprolactinemia by removing the inhibitory actions of dopamine on prolactin secretion. This results in amenorrhea, galactorrhea, and infertility in women and in loss of libido and impotence in men. Inhibition of the release of follicle-stimulating and luteinizing hormones may also play a role. In addition, weight gain is common, and food intake must be monitored. 

Mechanism of Action A dopamine agonist that directly stimulates dopamine receptors in the corpus striatum and inhibits prolactin secretion. Also suppresses secretion of growth hormone. Therapeutic Effect Improves symptoms of parkinsonism, suppresses galactorrhea, and reduces serum growth hormone concentrations in acromegaly. 

It is a peptide containing 14 amino acids and inhibits the release of growth hormone, TSH and prolactin from the pituitary and insulin and glucagon in pancreas. It has a very short plasma half-life. Because of its shorter duration of action and lack of specificity in inhibiting only GH secretion, its use in the treatment of acromegaly is limited. 

The role of cyclic AMP as modulator of prolactin secretion was first suggested by the finding of a stimulatory effect of cyclic AMP derivatives (17-22) and inhibitors of cyclic nucleotide phosphodiesterase activity such as theophylline and IBMX (22-26) on the secretion of this hormone. More convincing evidence supporting a role of cyclic AMP in the action of dopamine on prolactin secretion had to be obtained, however, by measurement of adenohypophysial adenylate cyclase activity or cyclic AMP accumulation under the influence of the catecholamine. As illustrated in Fig. 1, addition of 100 nM dopamine to male rat hemipituitaries led to a rapid inhibition of cyclic AMP accumulation, a maximal effect (30% inhibition) being already obtained 5 min after addition of the catecholamine. Thus, while dopamine is well known to stimulate adenylate cyclase activity in the striatum (27, 28), its effect at the adenohypophysial level in intact cells is inhibitory. Dopamine has also been found to exert parallel inhibitory effects on cyclic AMP levels and prolactin release in ovine adenohypophysial cells in culture (29) and purified rat mammotrophs (30). Using paired hemipituitaries obtained from female rats, Ray and Wallis (22) have found a rapid inhibitory effect of dopamine on cyclic AMP accumulation to approximately 75% of control. 

However, it is now known to exist in various nerve tracts and neuroendocrine tissues and it has general inhibitor actions. It can also inhibit release of other pituitary hormones (including thyroid-stimulating hormone (TSH) and prolactin). other endocrine hormones including pancreatic hormones (insulin and glucagon), peptide hormones from a variety of neuroendocrine tumours (e.g. VIPomas and glucagonomas) and also the release of most intestinal hormones. It is produced in the gut, the pancreas and in some peripheral nerves (see hypothalamic hormones PITUITARY hormones). Somatostatin is a cyclic peptide of 14 residues (SRIF-14) but is formed from a precursor of 28 residues (SRIF-28). 

Since prolactin has no target organ-inhibitory feedback system similar to those of TSH, ACTH, LH or FSH, it was proposed that high circulating levels of prolactin may inhibit the release of the hormone by the pituitary gland [251]. Ample experimental confirmation of this hypothesis has appeared in recent years. Either systemic injection or implantation of minute amounts of prolactin into the median eminence significantly reduces prolactin in the adenohypophysis and blood and inhibits mammary development and lactation in the rat. The inhibitory action of prolactin is believed to be exerted at the hypothalamic level since increases in hypothalamic PIF activity [252,253] and in the activity of the... 

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