EVIDENCE OF ANTAGONISM BETWEEN PROLACTIN AND GONADOTROPHIN SECRETION: EFFECT OF METHALLIBURE ON PERPHENAZINE-INDUCED PROLACTIN SECRETION IN OVARIECTOMIZED RATS

Abstract

SUMMARY Perphenazine has previously been shown to stimulate prolactin secretion in intact and to a lesser degree in ovariectomized virgin female rats. The question whether the oversecretion of gonadotrophins (follicle-stimulating hormone and luteinizing hormone) occurring in ovariectomized animals interferes with the ability of the pituitary cells to secrete prolactin was investigated in sham-operated and ovariectomized rats after separate and combined treatment with methallibure (ICI-33828, a non-steroidal gonadotrophin suppressor) and perphenazine which served as a prolactin releaser. Pituitary and serum prolactin were measured simultaneously by radioimmunoassay. Serum prolactin detected at the end of 5 days' treatment with perphenazine (5 mg/kg/day, s.c.) was found to be increased (81 ng/ml) compared with controls (29 ng/ml). Similar treatment given to ovariectomized animals increased serum prolactin levels from 13·7 ng/ml to only 27 ng/ml. Although high doses of methallibure alone (20 mg/kg/day, s.c.) given to ovariectomized rats for 17 days restored prolactin secretion to the levels occurring in intact non-treated animals, a dose of 10 mg was ineffective. However, when 10 mg methallibure were given to perphenazine-treated ovariectomized rats, serum prolactin rose again to 80·1 ng/ml. These results provide substantial evidence that, when the pituitary is secreting high amounts of gonadotrophin, its prolactin secretion is reduced and its ability to secrete prolactin after perphenazine challenge is limited. Once the gonadotrophic oversecretion is suppressed, more prolactin is secreted and the pituitary can again secrete high amounts of prolactin when challenged by perphenazine. The results show that in rats there exists an antagonism between gonadotrophin and prolactin secretion.