Dose-dependent suppression of postcastration luteinizing hormone secretion exerted by exogenous prolactin...

We examined the inhibitory effects of acute hyperprolactinemia on the postcastration rise in mean luteinizing hormone (LH) levels in adult male rats. The animals were administered purified ovine prolactin (oPRL) subcutaneously in a polyvinyl-pyrrolidone depot every 12 h for 96 h, beginning at the time of castration. oPRL suppressed postcastration LH secretion from 24 to 72 h when the effect spontaneously reversed in the face of elevated oPRL levels. oPRL suppressed postcastration LH secretion in a graded, dose-dependent fashion. The rats were administered increasing doses of oPRL and studied 48 h later, a time of maximal LH suppression. The first significant inhibition began in the high physiological range (about 200 ng/ml) and continued into the pathophysiological tumor range (about 2,500 ng/ml) of circulating oPRL levels. The highest oPRL levels markedly suppressed postcastration LH release. Autoregulatory feedback of oPRL on endogenous rat PRL secretion was examined in the dose-response study. It was striking to discover that PRL autofeedback appeared regulated as a threshold instead of a graded dose response and, more importantly, that the oPRL dose which produced the first significant suppression of LH secretion was the same dose which exerted PRL autofeedback. These findings indicate that postcastration LH secretion is inhibited by circulating PRL titers (about 200 ng/ml) which are above basal and stress-induced levels, but are within the range encountered during pregnancy, pseudopregnancy, and lactation. In addition, a common hypothalamic mechanism (perhaps dopaminergic), activated by elevated oPRL levels in this range, may inhibit both LH and rat PRL secretion.