Effect of Hyperprolactinemia on Pituitary Sensitivity to Luteinizing Hormone-Releasing Hormone Following Manipulation of Sex Steroids

Abstract

An inverse relationship between prolactin and gonadotropins has been recognized in humans as well as in experimental animals. The mechanism of such changes is poorly understood. In the present work, basal levels of serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH), and the response to LH-releasing hormone (LHRH) have been determined in intact and ovariectomized animals with hyperprolactinemia induced by perphenazine (5 mg/kg of body weight/day). Perphenazine significantly depressed basal LH and FSH levels in intact and castrated females. This depression could be due to lowered LHRH release by the hypothalamus, altered pituitary responsiveness to LHRH, or both. Hyperprolactinemia induced by perphenazine significantly depressed the pituitary LH response to LHRH in intact animals (P < 0.05). In castrated females treated with perphenazine, LHRH responsiveness was significantly increased (P < 0.05). In intact animals, perphenazine significantly increased serum progesterone levels (P < 0.05) but not estradiol levels. When progesterone (8 mg/kg of body weight/day) was injected after ovariectomy, perphenazine significantly depressed pituitary responsiveness to LHRH (P < 0.05). On the other hand, when 17 β -estradiol (1 μ g/kg of body weight/day) or 17 β -estradiol and progesterone was injected after castration. LHRH responsiveness was increased or unaltered, respectively. These results indicate that perphenazine induced a decreased release of hypothalamic LHRH resulting in gonadotropin suppression. In addition, in the intact animals, decreased pituitary sensitivity to LHRH also occurred as a result of increased progesterone secretion brought about by hyperprolactinemia.