Fibroblast growth factor as an intraovarian hormone: differential regulation of steroidogenesis by an angiogenic...

The potential role of fibroblast growth factor (FGF) in the regulation of granulosa cell differentiation was investigated because of its recent identification as the corpus luteum angiogenic factor. Treatment of rat ovarian granulosa cells with FGF inhibits the capacity of follicle stimulating hormone to stimulate estrogen production and to induce luteinizing hormone receptors. In contrast, although incubations with FGF can inhibit the estrogen-sensitive component of progesterone synthesis, the presence of FGF with suboptimal concentrations of follicle stimulating hormone significantly enhances the synthesis of progesterone. This capacity to differentially regulate steroidogenesis in the granulosa cell is comparable to the potency of FGF (ED50 = 30 pg/ml, 10(-12) M) in other in vitro assays. The observation that an angiogenic factor, like FGF, can specifically increase the sensitivity of progesterone synthesis and simultaneously inhibit estrogen formation supports the hypothesis that this growth factor plays an important role in the development and maintenance of a functional corpus luteum. As such, FGF may be involved in the local regulation of follicular selection, growth and atresia by simple virtue of its capacity to induce a neovascular response on one hand and by its ability to modulate the differentiated response to gonadotropins on the other.