Regulation of the FSH Receptor in the Ovary

The follicle-stimulating hormone receptor (FSHR) is found exclusively on granulosa cells from as early as the two-layer or primary stage of folliculogenesis. Up to four alternatively spliced transcripts have been described. An increase in steady-state levels of FSHR mRNA as well as a change in alternative splicing appear to be important during early folliculogenesis. FSHRs remain on the granulosa cells of healthy follicles until they become atretic or luteinize, with relatively little change in receptor number per cell. Factors that increase expression are FSH itself, cAMP and its analogs, activin and transforming growth factor beta (TGF-beta), whereas epidermal growth factor (EGF)/TGF-alpha decrease expression. The regulatory regions of the FSHR gene are more akin to 'housekeeping' genes than to a highly regulated gene, and there is an E box in the promoter region. Regulation of the initial expression of FSHR mRNA at the two-granulosa cell layer stage of folliculogenesis is not understood. It will also be important to understand whether the alternatively spliced FSHR transcripts and their prevalence in the ovary during early folliculogenesis represent a biologically important phenomenon.