GNRH EFFECTS ON LUTEAL FUNCTION DURING EARLY GESTATION

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The primary goal of this research proposal is to determine the locus or probably the loci of antifertility action of Gonadotropin Releasing Hormone (GnRN) and to understand the mechanism by which it suppresses the luteal progesterone production during early gestation (days 8-12 of pregnancy). Synthetic GnRH and its agonistic analog (GnRH ethylamide) will be used in this study. First, we will determine how the continuous infusion of GnRH or GnRH ethylamide by using the mini-somotic pump affects the plasma progesterone levels during early pregnancy. Throughout this study rats will be treated post-implanation, (days 7 through 12 of pregnancy). Next, we will examine the effects of GnRH or its analog on the luteal receptors for GnRH and LH and also on the plasma concentration of LH and Prolactin during early pregnancy. The next study is designed to determine whether GnRH or GnRH ethylamide suppresses testosterone (T) and estradiol (E2) production by the ovary; have an effect on the luteal concentration of receptors for E2 during the same period of gestation. Rats will be bled from the ovarian vein by cannulating it under ether anesthesia and the plasma will be stored frozen for the subsequent measurement of T and E2. Corpora lutea will be isolated for the measurement of E2 receptors. In the following study, it will be determined whether or not GnRH or its agonistic analog have any effect on the decidual luteotropin (DLt) and thus on progesterone secretion during this period. Finally, we will determine how the continuous infusion of GnRH or GnRH ethylamide affects the In Vitro synthesis of steroids by corpora lutea. Decidua bearing or untreated pseudopregnant rats will be hypophysectomized on day 8 of pseudopregnancy and will be given 0 or 1.5 of human Chorionic Gonadotropin (hCG) sc twice daily with simultaneous treatment with GnRH or its analog. Rats will be sacrificed on day 9, corpora will be isolated and incubated in medium 199 for 4 h at 37 C and their content of steroids will be measured to determine the net synthesis. It will also be examined whether or not this LH action is modulated by DLt or PRL. Understanding the mechanism by which GnRH affects the corpus luteum function in the rat will further stimulate research interests in women involving GnRH and antifertility effects due to its action on the ovary and/or placenta.