Reversal by human chorionic gonadotropin of the inhibitory effect of clomiphene on progesterone production by granulosa-luteal cells in culture.
The possibility of a direct ovarian effect of clomiphene citrate was assessed in vitro by measuring progesterone release from cultured human granulosa-luteal cells in both the presence and absence of hCG. Granulosa-luteal cells obtained by laparoscopic follicle aspiration following ovarian stimulation with hMG and hCG in women undergoing in vitro fertilization/embryo transfer were incubated for 72 hours in medium containing increasing concentrations of clomiphene (10(-9) - 10(-5) M) both without and with hCG (1 IU/mL). Clomiphene stimulated progesterone production in both the presence and absence of additional hCG at concentrations less than or equal to 10(7) M. In both the presence and absence of hCG a dose-dependent inhibition of progesterone production was observed with higher concentrations of clomiphene (greater than 10(6) M). hCG (1 IU/mL) significantly increased progesterone production in control cells and at all concentrations of clomiphene (10(-9)-10(-5) M) tested. Low clomiphene (10(-9)-10(-7) M) and hCG concentrations appeared to have a synergistic effect on progesterone production. Thus it appears that clomiphene has a direct ovarian effect on progesterone production, which is stimulatory at low concentrations and inhibitory at higher concentrations.
Lavy
G
G
Department of Obstetrics and Gynecology, Yale University School of Medicine, New Haven, Connecticut.
Diamond
M P
MP
Polan
M L
ML
D000328:Adult; D002478:Cells, Cultured; D006063:Chorionic Gonadotropin / Q000494:pharmacology*; D002996:Clomiphene / Q000494:pharmacology*; D003338:Corpus Luteum / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006107:Granulosa Cells / Q000378:metabolism*; D006801:Humans; D008184:Luteal Cells / Q000378:metabolism*; D010062:Ovulation Induction; D011374:Progesterone / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D011974:Receptors, LH / Q000187:drug effects
D006063:Chorionic Gonadotropin; D011974:Receptors, LH; D002996:Clomiphene; D011374:Progesterone