Keoxifene (LY 156758) inhibits follicle-stimulating hormone induced differentiation of cultured rat granulosa cells.
The direct effects of keoxifene (LY 156758), a benzothiphene-derived antiestrogen, on granulosa cell differentiation were examined in vitro using primary cultures of rat granulosa cells. The effect of keoxifene on FSH-stimulated aromatase activity was biphasic in pattern, enhancing at lower concentrations (up to 10(-8) M), and inhibiting at higher concentrations (greater than 10(-6) M). Keoxifene inhibited FSH-stimulated progestin production in a dose-dependent fashion with an IC50 of 5 X 10(-8) M. FSH-induced LH receptors were also inhibited by keoxifene with an IC50 of 5 X 10(-7) M. These findings suggest that keoxifene has direct pharmacologic actions at the ovarian level. In contrast to the earlier reported estrogenic actions of triphenylethylene antiestrogens at the ovarian level, the benzothiphene-derived antiestrogens may be clinically more useful in the management of estrogen-dependent malignancies.
D000818:Animals; D001141:Aromatase / Q000096:biosynthesis; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D004790:Enzyme Induction / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D005640:Follicle Stimulating Hormone / Q000494:pharmacology*; D006107:Granulosa Cells / Q000166:cytology*; D007700:Kinetics; D010880:Piperidines / Q000494:pharmacology*; D011374:Progesterone / Q000096:biosynthesis; D020849:Raloxifene Hydrochloride; D051381:Rats; D011919:Rats, Inbred Strains; D011974:Receptors, LH / Q000096:biosynthesis
D010880:Piperidines; D011974:Receptors, LH; D020849:Raloxifene Hydrochloride; D011374:Progesterone; D004958:Estradiol; D005640:Follicle Stimulating Hormone; D001141:Aromatase