An Explanation for Anovulation in Immature Alloxan-Diabetic Rats Treated with Pregnant Mare's Serum Gonadotropin: Reduced Pituitary Response to Gonadotropin-Releasing Hormone*

We have recently reported that immature alloxan- diabetic rats injected with PMS gonadotropin do not ovulate because the preovulatory LH surge is absent. In the present studies, the hypothesis was tested that alloxan-induced diabetes might alter hypothalamic gonadotropin-releasing hormone (GnRH) depletion and⁄or pituitary response to GnRH. Immature rats were injected with PMSG at 30 days of age. In one experiment, the rats were killed either before or during the expected proest-rous LH surge (day 32), and the hypothalami were removed and assayed for GnRH content. In other experiments, the effects of GnRH on ovulation and serum and pituitary LH were tested by injecting GnRH early on presumed proestrus (day 32). A significant and similar degree of depletion of hypothalamic GnRH was found in diabetic and control rats after the time of the expected LH surge in nondiabetic rats. Although the degree of pituitary exposure to endogenous GnRH is unknown, these data suggest that the hypothalamic release of GnRH is not significantly impaired by diabetes. The time of ovulation could be advanced by two injections of GnRH in control rats, in contrast to diabetic rats which ovulated only if given three injections of GnRH late in the afternoon of presumed proestrus. The pituitary response to a single injection of GnRH (as indicated by serum LH) was 3- to 4-fold greater in control rats than in diabetic rats. Pituitary LH concentrations were normal in diabetic rats on the morning of presumed proestrus and were not depleted after an injection of GnRH. It is concluded that the most likely explanation for anovulation and the loss of the preovulatory LH surge in diabetic rats is a decreased response of the pituitary to GnRH on presumed proestrus.