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Direct enhancement of gonadotropin-stimulated ovarian estrogen biosynthesis by estrogen and clomiphene citrate.

The biosynthesis of ovarian aromatases and hence estrogen production are under the control of the gonadotropins, FSH and LH. Using a primary culture of rat granulosa cells, we now report that estrogens (diethylstilbestrol and 17 beta-estradiol) augment the stimulation of aromatase activity by FSH and LH. Moreover, clomiphene citrate, a drug widely used to induce ovulation in anovulatory women, also enhances gonadotropin-stimulated aromatase activity. These in vitro findings suggest that estrogens within the microenvironment of the ovarian follicles may exert a local autoregulatory effect on their own production via an ultra-short loop, positive feedback mechanism. In addition, the clinical efficacy of clomiphene citrate may derive partially from its direct augmentation of the gonadotropin-stimulated estrogen production at the ovarian level.