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Inhibition of androgen and oestrogen production by clomiphene citrate in avian theca cells

Summary. Isolated theca cells (2 x 10⁵/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.