Regulation of human granulosa-luteal cell progesterone production and proliferation by gonadotropins and growth factors.

The effects of human chorionic gonadotropin (hCG), follicle-stimulating hormone (FSH), fibroblast growth factor (FGF), and epidermal growth factor (EGF) on human granulosa-luteal cell proliferation and progesterone (P) production were studied in vitro. The cells were obtained from an in vitro fertilization protocol and were cultured for 2 to 12 days on plastic culture dishes or on dishes coated with extracellular matrix (ECM). During the first 2 to 4 days of culture, basal P production was high and could not be further stimulated with gonadotropins. Thereafter, basal P production decreased and could be stimulated by both hCG and FSH. The cells growing on ECM produced less P than the cells growing on plastic. EGF and FGF significantly increased cell proliferation on both substrates. FGF did not influence P production, while EGF clearly increased basal P production of the cells cultured on plastic. The high P production in cultured human granulosa cells obtained from follicles stimulated in vivo indicates that at least some of the cells were luteinized. The present data also demonstrate that EGF and FGF are mitogenic for human granulosa-luteal cells, and EGF regulates their biosynthesis in vitro. These results suggest that growth factors may also regulate granulosa cell function in vivo.