Date of Award


Degree Type


Degree Name

Doctor of Philosophy


This study examines the role of androgen in the regulation of FSH-induced aromatase activity in rat granulosa cells in vitro. Experiments were designed to determine whether androgens act solely as substrates for FSH-induced aromatase activity or whether they also participate in the mechanism by which FSH increases the activity of the enzyme.;Granulosa cells were isolated from ovaries of immature rats and cultured during a 36- to 60-h "induction period" in the presence or absence of FSH with or without steroids and/or other compounds. Cells were then incubated for a further 6- and 12-h "test period" with aromatizable substrate (testosterone). Accumulation of estrogen in culture medium during the test period was measured as an indirect index of aromatase activity stimulated by treatments during the induction period.;In the absence of FSH during the induction period, conversion of testosterone to estrogen during the test period was very low. Culturing with FSH alone during the induction period significantly increased aromatase activity. Presence of androgen during the induction period enhanced the ability of FSH to induce enzyme activity. Both aromatizable and nonaromatizable androgens were effective indicating that androgen action was not dependent upon their conversion to estrogen. Hydroxyflutamide (an antiandrogen known to block androgen-receptor interaction) during the induction period inhibited the stimulatory effects of androgens.;In addition to FSH, (Bu)(,2)cAMP and 8-BrcAMP induced aromatase activity, however, the effect of cAMP analogues was not enhanced by androgen. During culture, granulosa cell responsiveness to FSH (measured as the ability of FSH to stimulate cAMP production), FSH binding capacity and FSH receptor affinity decreased. Culturing with androgens prevented the loss of responsiveness and receptor affinity, but not binding capacity.;The results of this study suggest that androgens regulate estrogen production by granulosa cells not only by acting as substrates for FSH-induced aromatase, but also by participating in the mechanism by which FSH increases activity of the enzyme. This action of androgen is androgen receptor-mediated and is exerted at some step prior to cAMP production, possible at the level of the FSH receptor.



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