GnRH action on luteal steroidogenesis during pregnancy

The results of our study presented here establishes that gonadotropin-relea sing hormone (GnRH) acts directly on the corpus luteum, leading to suppress ed production and release of progesterone and thus disrupting pregnancy. A GnRH-agonist (GnRH-Ag) treatment suppressed the luteal and serum progestero ne levels. This suppression is neither mediated by a fall in ovarian testos terone production nor its conversion to estradiol. Although the treatment s uppressed the nuclear estradiol-receptor content and binding sites for LH i n the corpus luteum, it had no effect on the luteal binding sites for GnRH and prolactin within 24 h. GnRH-Ag augmented the plasma levels of luteinizi ng hormone, decreased the magnitude of nocturnal surges of prolactin, and h ad no effect on luteal cyclic adenosine 5'-monotriphosphate levels. Yet, th e treatment had no effect on the luteal content of free cholesterol. We hav e also demonstrated, for the first time, the presence of steroidogenic acut e regulatory protein and peripheral benzodiazepine receptor in the rat corp us luteum, and the suppression of these proteins by GnRH-Ag leads to reduce d steroidogenesis by the corpus luteum. Concomitantly, P450 side-chain clea vage enzyme, its activity, and its mRNA content and 3 beta-hydroxy-steroid dehydrogenase content in die corpus luteum decreased. The treatment suppres sed the plasma levels of pregnenolone and 20 alpha-dihydroprogesterone. The se data suggest that the suppression of luteal steroidogenesis by GnRH-Ag m ay be due: to its inhibitory effect on the cholesterol transport and/or on the enzymes involved in the steroidogenic pathway. Furthermore, based on ot her observations made in our laboratory, we propose a hypothesis that an en dogenous GnRH is present in the corpus luteum/ovary during pregnancy in the rat and that this GnRH may play a physiological role in the regulation, ma intenance, and/or termination of pregnancy. (C) 1999 Elsevier Science Inc. All rights reserved.