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 development. We have examined the effects of FSH and activin on FSH receptor mRNA in cultured rat granulosa cells. Treatment of granulosa cells with FSH resulted in transient suppression of the FSH receptor mRNA levels 2-6 h after treatment, with subsequent recovery at 24 h. We could not detect a similar effect on FSH receptor mRNA by 8-bromoadenosine 3,5-cyclic monophosphate, which continuously stimulated FSH receptor mRNA over a similar time course. On the other hand, stimulation of the protein kinase C (PKC) pathway with phorbol myristate acetate mimicked the time course of the effects of FSH on the levels of FSH receptor mRNA. Taken together, these results suggest that the cAMP cascade may increase the mRNA levels of FSH receptor and, at the same time, the other cascade, PKC, may decrease FSH receptor mRNA levels. To further investigate the role of activin in the regulation of granulosa cell function, we studied the effect of activin on FSH receptor mRNA levels. Compared to the control, treatment with activin (100 ng/ml) increased FSH receptor mRNA in a time-dependent manner with a maximum circa 4-fold increase at 24 h. Treatment of granulosa cells with activin (20-300 ng/ml) for 24 h increased FSH receptor mRNA in a dose-dependent manner to a maximum circa 4-fold increase at concentrations of 100-300 ng/ml. Although follistatin alone had no detectable effect on FSH receptor mRNA levels, combination of follistatin (0-200 ng/ml) with activin (100 ng/ml) caused a significant reduction in the levels of activin-induced FSH receptor mRNA in a dose-dependent manner.