Prolactin secretion derivatives

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. 

Secondly ergot derivatives which reveal a clearcut agonistic activity on prolactin secretion and as antiparkinson agents (20) were inactive on the cyclase. Surprisingly, lisuride and lergotrile were found to be weak antagonists of dopamine stimulated cAMP accumulation, but they could also antagonize the cAMP production stimulated by isoproterenol as... 

In my opinion, one may assume a priori that these criteria will not be fulfilled first, if the dopamine-sensitive adenylate cyclase was really involved in the parathormone secretion, the patients treated with neuroleptics and especially with the most potent drugs on the sites (phenothiazine and thioxanthene derivatives) would have normally revealed marked changes in their parathormone secretion, just like as is the case for the prolactin secretion in fact such changes have never been observed secondly, a recent report clearly indicates that the injection of dopamine in man does not modify parathormone secretion although a marked decrease in prolactin was observed (21). There is no receptor without physiological response the study of receptor requires a multidisciplinary approach. 

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. 

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. 

F. Prolactin-Inhibiting Hormone (PIH, Dopamine) Dopamine is the physiologic inhibitor of prolactin release. Because of its peripheral effects and the need for parenteral administration, dopamine is not useful in the control of hyperprolactinemia, but bromocriptine and other orally active ergot derivatives (eg, cabergoline. pergolide) are effective in reducing prolactin secretion from the normal gland as well as from pituitary tumors. 

Recent interest in lergotrile (33) (Figure 7) stems from its putative dopaminergic activity and inhibition of prolactin secretion. Toxicity in clinical trials prompted the exploration of microbial transformation for producing less toxic derivatives. 

Selected from a group of dihydolysergylurea derivatives for its outstanding pharmacological and pharmacodynamic activi, carbergoline (232) has been used fw its significant prolactin secretion inhibitory activity. This compound... 

Anterior pituitary hormones include growth hormone (GH), thyrotropin (TSH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), and adrenocorticotropin (ACTH). Another peptide, B-lipotropin (B-LPH), is derived from the same prohormone, proopiomelanocortin, as ACTH. B-LPH is secreted from the pituitary (along with ACTH), and is a precursor of the opioid peptide B-endorphin (see Chapter 31 Opioid Analgesics Antagonists). 

The direct actions of DA on pituitary hormone secretion are largely inhibitory, maintaining basal secretion of prolactin from anterior pituitary lactotrophs and POMC-derived peptide hormones from intermediate lobe melanotrophs via inhibitory D2 receptors located on these cells. Episodic surges of these hormones are associated with... 

A hypersecretion of the hormone is generally implicated in the pathogenesis of the polypeptide-hormone-derived amyloids (Westermark 1994). The pituitary gland can maintain a prolactin secretory capacity at old age (Rolandi et al. 1982), and age per se does not seem to alter the rate of secretion of prolactin in humans (Yamaji et al. 1976), nor is the circadian rhythms of prolactin plasma levels modified at old age (Touitou et al. 1981). 

Hormoproteins.—Several of the internal secretions of the human body have been found to be proteins or protein derivatives. Chief among these protein hormones are insulin, secretin, thyro-globulin, prolactin and other pituitary factors, parathyrin. The simple autaooids, adrenaline and thyroxine are amino acid derivatives. 

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