GONADOTROPIN-RELEASING HORMONE-INDUCED DESENSITIZATION MAY ACCOUNT FOR THE DECREASE IN PITUITARY-RESPONSIVENESS AFTER THE PREOVULATORY LUTEINIZING-HORMONE SURGE

The LH secretory response of gonadotropes to GnRH varies during the es trous cycle of the rat. The increased secretion of estrogens during th e 24-48 h before the preovulatory surge of LH secretion and the enhanc ed quantities of progesterone secreted acutely during the surge elevat e the responsiveness of hypophysial gonadotropes to GnRH. However, the cause of the massive decline in GnRH responsiveness that occurs durin g or after the surge remains unknown. In the present studies, we inves tigated the possibility that it is due to GnRH-induced desensitization of gonadotropes. Dispersed pituitary cells from proestrous and estrou s rats were preincubated with GnRH (3 or 6 h, 10(-10) or 10(-9) M), pr ogesterone (13 h, 100 or 200 nM), GnRH plus progesterone, or medium al one. Then, the cells were retrypsinized to permit performance of the r everse hemolytic plaque assay for measurement of LH secretion, during which they were treated with GnRH (0, 10(-11), 10(-10), and 10(-8) M) for 2 h. The cells from estrous animals showed the large decline in Gn RH responsiveness typical of that day of the cycle compared to those f rom proestrous animals (the total amount of LH secreted decreased by 5 0-70%). Preincubation of cells from proestrous rat pituitary glands wi th GnRH in concentrations and for durations that were designed to mimi c the physiological situation induced a decline in GnRH responsiveness similar to that observed at estrus. Preincubation with progesterone a lso reduced the pituitary responsiveness to GnRH in a dose-dependent m anner, but did not show additive effects with GnRH. Our results sugges t that the major increase in GnRH secretion that induces the preovulat ory surge of LH secretion may also participate in inducing the major d ecrease in pituitary responsiveness to GnRH that occurs from proestrus to estrus.