No abstract

Feedback regulation of basal and stimulated release of prolactin (Prl) was studied in primary cultures of rat pituitary cells and in adult male rats bearing right atrial catheters. Exposure of cell cultures to ovine (o) Prl, which does not crossreact in the radioimmunoassay for rat (r) Prl, did not affect rPrl release during in vitro incubations. oPrl, 4 mg/kg, injected subcutaneously into male rats 4 h previously, significantly suppressed basal rPrl levels and blunted the rPrl response to ether (2 min), cimetidine (25 mg/kg i.v.), thyrotropin-releasing hormone (40 or 400 ng i.v.), or a low dose of metoclopramide (25 µg/kg i.v.). At a higher dose of metoclopramide (500 µg/kg i.v.), no effect of oPrl could be observed. These data support the hypothesis that Prl feedback control occurs within the central nervous system rather than at the pituitary and involves predominantly, if not exclusively, a dopaminergic mechanism.

The present studies were performed in order to determine whether the inhibition of prolactin (Prl) secretion which follows the systemic administration of L-dopa and its conversion to dopamine (DA) is mediated by central or by peripheral mechanisms. The effects of pretreatment with the dopa-decarboxylase inhibitor MK-486 (L-α-methyldopa-hydrazide) on the L-dopa and DA inhibition of Prl secretion and on dopa-decarboxylase activity in anterior pituitary, hypothalamus, cerebral cortex and adrenal medulla were evaluated in rats using a dose reported to cause peripheral but not central dopa-decarboxylase inhibition. I.v. infusions of DA, 1 and 10 µg/kg/min, and of L-dopa, 0.1 and 1 mg/kg/min for 15 min, suppressed plasma Prl levels as well as the Prl release response to 0.2 porcine stalk median eminence equivalents (pSME). I.p. administration of MK-486, 50 mg/kg, 30 min before the infusion of L-dopa did not alter either basal or pSME-stimulated Prl secretion or the inhibitory effect of L-dopa. Dopa-decarboxylase activity in the anterior pituitary and the adrenal medulla was completely inhibited by MK-486, while hypothalamic and cerebral cortex dopa-decarboxylase activity was reduced 85 and 84%, respectively. Since dopa conversion to DA could not have occurred peripherally in the presence of MK-486, the results indicate that the residual dopa-decarboxylase activity within the central nervous system (CNS) was capable of permitting sufficient conversion of L-dopa to DA to inhibit Prl secretion. These results provide evidence that L-dopa is capable of exerting its suppressive action on Prl secretion when its decarboxylation to DA is restricted to CNS sites.