Susceptibility of ovarian granulosa cells to apoptosis differs in cells isolated before or after the preovulatory LH surge.

The luteinizing hormone (LH) surge initiates the final stages of ovarian follicle development, and induces ovulation and luteinization of preovulatory follicles. To investigate whether exposure to the LH surge alters follicle cell susceptibility to apoptosis, granulosa and theca cells were isolated from bovine preovulatory follicles before and 14 h after injection of GnRH to induce an LH surge. Granulosa cells isolated before the LH surge were susceptible to apoptosis induced by soluble Fas ligand or serum withdrawal, while cells isolated after the LH surge were resistant to apoptosis. Resistance to Fas-mediated apoptosis was not associated with decreased Fas mRNA or protein levels. Pretreatment of granulosa cells isolated after the LH surge with the protein synthesis inhibitor cycloheximide rendered the cells susceptible to Fas-mediated apoptosis, indicating that inhibition of apoptosis was mediated by expression of labile survival factors. Theca cells were sensitive to Fas-mediated apoptosis before and after exposure to the LH surge. Resistance to apoptosis of granulosa cells from preovulatory follicles after the LH surge may be important for normal ovulation and luteinization.