Suppression of Luteal Production of Progesterone In Vitro by GnRH Agonist During Pregnancy

Abstract

Previous studies from this laboratory have demonstrated that in vivo treatment with a gonadotropin-releasing hormone agonist (GnRH-Ag) suppresses luteal progesterone (PR) synthesis in pregnant rats within 24 h, with no effect on the ability of the luteal synthesis of testosterone or estradiol (1, 2). Although PR secretion is acutely stimulated by luteinizing hormone (LH) during early pregnancy, the constant high titers of PR necessary to maintain pregnancy in the rat appear to be the result of indirect LH action through testosterone that is aromatized to estradiol by the corpus luteum (3). Recently, we observed, in pregnant rats treated with GnRH-Ag at the level of luteal ultrastructure, an increase in the number of lipid droplets and a decrease in the number of tubular cristae within the mitochondria (4). In addition, the in vivo GnRH-Ag treatment decreased the luteal P-450 sidechain cleavage (P-450SCC) enzyme and mRNA content (5). These observations suggest that the in vivo treatment of GnRH-Ag within the corpus luteum inhibits PR synthesis by decreasing the amount of P-450SCC mRNA and enzyme content, which may alter the mitochondrial cristae structure. Collectively, these data indicate that the effect of GnRH-Ag in the pregnant rat may be due to its direct inhibitory action on luteal steroidogenesis. However, this has not been tested yet. Therefore, the purpose of this study was to determine if the in vitro GnRH-Ag treatment during early pregnancy has any suppressive effect on luteal steroidogenesis by utilizing an in vitro model system.