Effects of Fibroblast Growth Factors and the Transcription Factor, Early Growth Response 1, on Bovine Theca Cells

The theca cell layer of the ovarian follicle secretes growth factors that impact the function of granulosa cells. One such factor is fibroblast growth factor 18 (FGF18) that causes apoptosis of granulosa cells, however it is not known if FGF18 induces apoptosis also in theca cells. Addition of recombinant FGF18 to bovine theca cells in vitro inhibited steroidogenesis but, in contrast to previous data in granulosa cells, decreased the incidence of apoptosis. FGF18 activated typical FGF signaling pathways in theca cells, which was not previously observed in granulosa cells. The transcription factor Early Growth Response-1 (EGR1) was a target of FGF18 action; overexpression and knock-down experiments demonstrated that EGR1 is a major upstream component of FGF signaling in theca cells and that it directs cell fate toward proliferation. These data suggest that FGF18 is mitogenic for theca cells while being pro-apoptotic in granulosa cells.