Inhibition of androgen and oestrogen production by clomiphene citrate in avian theca cells.
Isolated theca cells (2 X 10(5)/ml) were pre-incubated for 1 h in the presence or absence of clomiphene citrate (10(-12)-10(-4) M). Ovine LH (50 ng/ml) was added and cells were incubated for an additional 3 h. A 50% inhibition of LH-stimulated androstenedione and oestrogen production was obtained with doses of 10(-8) M and 2 X 10(-7) M clomiphene, respectively. Furthermore, the effect of clomiphene on LH-stimulated androstenedione production was reversed by washing clomiphene from the cells before stimulation with LH. In subsequent experiments, the effects of clomiphene on C17-20-lyase and aromatase activities were examined. Conversion of [3H]17-hydroxyprogesterone to androstenedione was inhibited by 50% when theca cells were pretreated with 10(-5) M-clomiphene. In addition, conversion of testosterone to oestrogen by theca cells was inhibited in a dose-dependent manner by clomiphene, with 50% inhibition occurring at a dose of 5 X 10(-6) M. The results show that clomiphene treatment in vitro inhibits androgen and oestrogen production in theca cells by inhibitory effects on the activities of C17-20-lyase and aromatase. In addition to the widely-accepted effects of clomiphene on the hypothalamic-pituitary axis, the present findings add further support to the suggestion that clomiphene exerts direct effects on ovarian steroidogenesis.
D000446:Aldehyde-Lyases / Q000378:metabolism; D000735:Androstenedione / Q000096:biosynthesis*; D000818:Animals; D001141:Aromatase / Q000378:metabolism; D002645:Chickens; D002996:Clomiphene / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004967:Estrogens / Q000096:biosynthesis*; D005260:Female; D066298:In Vitro Techniques; D007986:Luteinizing Hormone / Q000494:pharmacology; D013254:Steroid 17-alpha-Hydroxylase; D013799:Theca Cells / Q000187:drug effects* / Q000378:metabolism
D004967:Estrogens; D002996:Clomiphene; D000735:Androstenedione; D007986:Luteinizing Hormone; D001141:Aromatase; D013254:Steroid 17-alpha-Hydroxylase; D000446:Aldehyde-Lyases