Direct effects of clomiphene citrate on the steroidogenic capability of human granulosa cells.
The effects of clomiphene citrate (CC), 17 beta-estradiol (E2), and human chorionic gonadotropin (hCG) on the accumulation of progesterone (P) and 20 alpha-hydroxy-4-pregnen-3-one (20 alpha-OHP) in cultured human granulosa cells (GC) were examined. In addition, the metabolism of [4-14C]pregnenolone and accumulation of [4-14C]P in response to CC and E2 were determined. The authors conclude the following: (1) the dose-dependent inhibition of P and 20 alpha-OHP production by CC in GC was not reproduced by E2, (2) hCG abolished these effects of CC, (3) these inhibitory actions of CC were not associated with altered 3 beta-hydroxysteroid dehydrogenase activity nor P catabolism indicating that, (4) these actions by CC on the GC occur at some step(s) during steroidogenesis preceding the formation of pregnenolone. These findings may explain, at least in part, the luteal deficiency experienced by women treated with CC, and they also provide a rationale for the use of hCG supplementation during ovulation induction with CC.
Yuen
B H
BH
Department of Obstetrics and Gynecology, University of British Columbia, Grace Hospital, Vancouver, Canada.
Mari
N
N
Duleba
A J
AJ
Moon
Y S
YS
D004092:20-alpha-Dihydroprogesterone / Q000096:biosynthesis*; D000328:Adult; D002478:Cells, Cultured; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D002996:Clomiphene / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D006107:Granulosa Cells / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D011284:Pregnenolone / Q000378:metabolism; D011374:Progesterone / Q000031:analogs & derivatives* / Q000096:biosynthesis*
D006063:Chorionic Gonadotropin; D004092:20-alpha-Dihydroprogesterone; D002996:Clomiphene; D011374:Progesterone; D004958:Estradiol; D011284:Pregnenolone