Inhibitory feedback effects of prolactin on its secretion involve central nervous system dopaminergic mediation

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 micrograms/kg i.v.). At a higher dose of metoclopramide (500 micrograms/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.