REGULATION OF FOLLICLE-STIMULATING-HORMONE RECEPTOR

The acquisition of follicle-stimulating hormone (FSH) receptors during folliculogenesis is believed to be a key event in follicle developmen t. We have examined the effects of FSH and activin on FSH receptor mRN A in cultured rat granulosa cells. Treatment of granulosa cells with F SH resulted in transient suppression of the FSH receptor mRNA levels 2 -6 h after treatment, with subsequent recovery at 24 h. We could not d etect a similar effect on FSH receptor mRNA by 8-bromoadenosine 3,5-cy clic monophosphate, which continuously stimulated FSH receptor mRNA ov er a similar time course. On the other hand, stimulation of the protei n kinase C (PKC) pathway with phorbol myristate acetate mimicked the t ime course of the effects of FSH on the levels of FSH receptor mRNA. T aken together, these results suggest that the cAMP cascade may increas e the mRNA levels of FSH receptor and, at the same time, the other cas cade, PKC, may decrease FSH receptor mRNA levels. To further investiga te the role of activin in the regulation of granulosa cell function, w e studied the effect of activin on FSH receptor mRNA levels. Compared to the control, treatment with activin (100 ng/ml) increased FSH recep tor mRNA in a time-dependent manner with a maximum circa 4-fold increa se at 24 h. Treatment of granulosa cells with activin (20-300 ng/ml) f or 24 h increased FSH receptor mRNA in a dose-dependent manner to a ma ximum circa 4-fold increase at concentrations of 100-300 ng/ml. Althou gh follistatin alone had no detectable effect on FSH receptor mRNA lev els, combination of follistatin (0-200 ng/ml) with activin (100 ng/ml) caused a significant reduction in the levels of activin-induced FSH r eceptor mRNA in a dose-dependent manner.