Uterus of the rat contains prolactin inhibitory activity

Activity found in crude acid extracts of uterine tissue obtained from pseudopregnant, proestrous, or ovariectomized rats causes a dose-dependent inhibition of prolactin (PRL) release with a concurrent intracellular accumulation of PRL by anterior pituitary cells in culture. The absence of any significant effects imposed by the uterine extracts on basal luteinizing hormone or follicle-stimulating hormone secretion in these same cultures suggests that the activity is a noncytotoxic inhibitor of PRL secretion. Furthermore, failure of uterine extracts to degrade standard rat PRL after a 24-h coincubation at 37 degrees C suggests that the inhibitory activity is also nonproteolytic. That the activity is tissue specific is supported by the fact that extracts of gut, cardiac muscle, and diaphragm failed to block PRL release, whereas similarly prepared uterine extracts retained the ability to significantly depress PRL secretion. Haloperidol or bicuculline, dopaminergic and GABAergic receptor blockers, respectively, were ineffective in reversing the inhibitory effects of uterine extract on PRL secretion, suggesting that the inhibition is not due to dopamine or GABA. In addition to affecting basal release of PRL, in vitro larger doses of uterine extract were able to reverse the stimulatory effects of thyrotropin-releasing hormone on PRL secretion, indicating that the uterine-derived PRL inhibitory activity may also regulate stimulated PRL release. Taken together, these findings support the existence of a nondopaminergic, non-GABAergic inhibitory factor of uterine origin that specifically suppresses basal and stimulated secretion of PRL from cultured anterior pituitary cells.