Follicle-stimulating hormone induces terminal differentiation in a predifferentiated rat granulosa cell line (ROG)

The divergent commitment of ovarian granulosa cells to either proliferation and differentiation or programmed cell death directly reflects the process of follicular dominance and atresia. This process is regulated by FSH and local paracrine factors. To further analyze the role of FSH and intraovarian factors in follicular selection, we have established a rat ovarian granulosa (ROG) cell line from prepubertal (p14) rats. ROG cells are cultured in serum-free medium with activin A, but without FSH. ROG cells bind FSH and respond to FSH by a burst of cell proliferation and increased progesterone secretion. These results support the hypothesis that activin, but not FSH, is an important factor in the maintenance of immature granulosa cells. After exposure of ROG cells to FSH, withdrawal of FSH from the cultures results in apoptotic tell death. ROG cells start active membrane blebbing by 2 h after FSH withdrawal, and most cells die within 7 h. Thus, FSH-induced ROG cells differentiate into a more mature granulosa phenotype, which is nonmitotic and dependent on FSH for survival. The ROG cell line may thus provide a good in vitro model of follicular selection.