GnRH action on luteal steroidogenesis during pregnancy.
The results of our study presented here establishes that gonadotropin-releasing hormone (GnRH) acts directly on the corpus luteum, leading to suppressed production and release of progesterone and thus disrupting pregnancy. A GnRH-agonist (GnRH-Ag) treatment suppressed the luteal and serum progesterone levels. This suppression is neither mediated by a fall in ovarian testosterone production nor its conversion to estradiol. Although the treatment suppressed the nuclear estradiol-receptor content and binding sites for LH in 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 luteinizing hormone, decreased the magnitude of nocturnal surges of prolactin, and had no effect on luteal cyclic adenosine 5'-monotriphosphate levels. Yet, the treatment had no effect on the luteal content of free cholesterol. We have also demonstrated, for the first time, the presence of steroidogenic acute regulatory protein and peripheral benzodiazepine receptor in the rat corpus luteum, and the suppression of these proteins by GnRH-Ag leads to reduced steroidogenesis by the corpus luteum. Concomitantly, P450 side-chain cleavage enzyme, its activity, and its mRNA content and 3beta-hydroxy-steroid dehydrogenase content in the corpus luteum decreased. The treatment suppressed the plasma levels of pregnenolone and 20alpha-dihydroprogesterone. These data suggest that the suppression of luteal steroidogenesis by GnRH-Ag may be due to its inhibitory effect on the cholesterol transport and/or on the enzymes involved in the steroidogenic pathway. Furthermore, based on other observations made in our laboratory, we propose a hypothesis that an endogenous 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, maintenance, and/or termination of pregnancy.
Sridaran
R
R
Department of Physiology, Morehouse School of Medicine, Atlanta, Georgia 30310-1495, USA. sridaran@msm.edu
Lee
M A
MA
Haynes
L
L
Srivastava
R K
RK
Ghose
M
M
Sridaran
G
G
Smith
C J
CJ
D000595:Amino Acid Sequence; D000818:Animals; D003338:Corpus Luteum / Q000378:metabolism*; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*; D006727:Hormone Antagonists / Q000494:pharmacology; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000378:metabolism*; D011374:Progesterone / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley
D006727:Hormone Antagonists; D007987:Gonadotropin-Releasing Hormone; D011374:Progesterone; C030741:lutrelin acetate