Prolactin secretion inhibition

Stimulates prolactin secretion Inhibits prolactin secretion... 

The release of prolactin from the adenohypophysis is normally inhibited by prolactin-inhibiting hormone (PIH, dopamine) from the hypothalamus. Prolactin secretion is also controlled by prolactin-releasing factor (PRF). The release of PRF from the hypothalamus is mediated by reflexes elicited by suckling and breast stimulation. 

The answer is d. (Hardman, pp 1371-13720 High prolactin levels in the serum result in amenorrhea, for reasons that are not known. Bromocriptine inhibits prolactin secretion through its dopaminergic action This compound, a semisynthetic ergot derivative, appears to be a dopamine receptor agonist. It is administered orally to the patient and, in most cases, menses occurs after a month of therapy. 

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... 

They have a low incidence of adverse reactions and the reactions that occur are generally mild. Rapid intravenous infusion of H2 antagonists may cause bradycardia. Cimetidine is more inclined to cross the blood-brain barrier and CNS effects such as somnolence and confusion have been described, especially in the elderly and in patients with impaired renal function. Cimetidine in high doses, as the only one of its class, has antiandrogenic effects which could be explained by an increase of prolactin secretion, binding to androgen receptors and inhibition the cytochrome P450 mediated hydroxylation of estradiol. 

LaBella FS, Dular R, Lemon P, et al. 1973. Prolactin secretion is specifically inhibited by nickel. Nature 245 330-332. 

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. 

Prolactin secretion is under the inhibitory control of hypothalamus through prolactin inhibiting hormone (PRIH) which is a dopamine and acts on pituitary lactotrope receptor. 

The most common undesirable effect of methyldopa is sedation, particularly at the onset of treatment. With long-term therapy, patients may complain of persistent mental lassitude and impaired mental concentration. Nightmares, mental depression, vertigo, and extrapyramidal signs may occur but are relatively infrequent. Lactation, associated with increased prolactin secretion, can occur both in men and in women treated with methyldopa. This toxicity is probably mediated by inhibition of dopaminergic mechanisms in the hypothalamus. 

No preparation of prolactin is available for use in prolactin-deficient patients. For patients with symptomatic hyperprolactinemia, inhibition of prolactin secretion can be achieved with dopamine agonists, which act in the pituitary to inhibit prolactin release. 

A 56-residue peptide, which is formed from the 10-kDa precursor to GnRH, inhibits secretion of prolactin.75 Inhibition of FSH release is accomplished by feedback inhibition. Hormones known as inhibins are produced in the gonads and act to inhibit release of FSH from the pituitary.76... 

FIGURE 10—13. The tuberoinfundibular dopamine pathway from hypothalamus to anterior pituitary regulates prolactin secretion into the circulation. Dopamine inhibits prolactin secretion. 

Serotonin 2A antagonism may reverse dopamine 2 antagonism in the tuberoinfundibular pathway. There is an antagonistic and reciprocal relationship between serotonin and dopamine in the control of prolactin secretion from the pituitary lactoroph cells. That is, dopamine inhibits prolactin release by stimulating D2 receptors (Fig. 11—30), whereas serotonin promotes prolactin release by stimulating 5HT2A receptors (Fig. 11—31). 

Feek CM, Sawers JS, Brown NS, Seth J, Irvine WJ, Toft AD. Influence of thyroid status on dopaminergic inhibition of thyrotropin and prolactin secretion evidence for an additional feedback mechanism in the control of thyroid hormone secretion. J Clin Endocrinol Metab 1980 51(3) 585-9. 

Dopamine agonists decrease pituitary prolactin secretion through a dopamine-mimetic action on the pituitary at two central nervous system loci (1) they decrease dopamine turnover in the tuberoinfundibular neurons of the arcuate nucleus, generating increased hypothalamic dopamine and (2) they act directly on pituitary dopamine receptors to inhibit prolactin release. 

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. 

As much as higher concentrations of dopamine are required to stimulate striatal adenylate cyclase activity as compared to the affinity of the drug for the agonistic sites of the receptor, the sensitivity of the anterior pituitary adenylate cyclase to dopamine agonists in both human prolactinoma (26) and rat adenohypophysial homogenate (31) is lower than the potency of the compounds to inhibit prolactin secretion in intact cells (2). This variable loss of sensitivity upon cell homogeneization is a phenomenon frequently observed in other systems (32). 

Since cyclic AMP derivatives and inhibitors of cyclic nucleotide phosphodiesterase stimulate prolactin release (17, 37, 38) and dopamine is a potent inhibitor of prolactin secretion (1, ly 39), it is not surprising that the catecholamine does not stimulate the adenylate cyclase system. On the contrary, the data summarized above show that the pituitary DA receptor is negatively coupled to adenylate cyclase. The pituitary DA receptor is thus a typical DA -receptor (40, 41). In view of the multiplicity of factors involved in the control of prolactin secretion, including sex steroids, it is likely that mechanisms other than cyclic AMP are involved (39, 42). It does however appear that inhibition of cyclic AMP formation by dopamine is a key element in a multifactorial control system responsible for the fine tuning of prolactin secretion. 

Rm did not correlate with the intrinsic activity of agonists for their ability to attenuate adenylate cyclase stimulation (36).In that system, only the ratio of K./K appeared to correlate with the intrinsic activity ofLthe alpha-adrenergic agonists. Here, in anterior pituitary membranes constant proportions of both receptor states were evidenced but ratios of 30-200 were found for K./Km for a series of dopaminergic agonists despite the fact that these agonists all appear to display full intrinsic activity in their ability to inhibit prolactin secretion from pituitary cells. 

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