An ovulatory gonadotropin stimulus increases cytosolic phospholipase A2 expression and activity in granulosa cells of primate periovulatory follicles

Context: Prostaglandins (PGs) produced within ovarian follicles in response to the ovulatory gonadotropin surge are essential for follicle rupture and oocyte release. Arachidonic acid, the common precursor for PG synthesis, is cleaved from membrane phospholipids via the activity of phospholipase A2 (PLA2). Objective: The purpose of this study was to determine which PLA2 form(s) is involved in PG production by primate periovulatory follicles. Design and Interventions: Gonadotropins were administered to cynomolgus monkeys to stimulate multiple follicular development; human chorionic gonadotropin (hCG) initiated periovulatory events. Granulosa cells and whole ovaries were obtained before (0 h), and 12, 24, and 36 h after hCG administration. Patients: Granulosa-lutein cells were also obtained from women undergoing infertility treatment. Outcome Measures and Results: mRNA for cytosolic (c)PLA2 and secretory (s)PLA2V, but not sPLA2IIA, was expressed by granulosa cells. cPLA2 mRNA levels were low at 0 h, elevated by 12 h, and remained high 24-36 h after hCG administration. sPLA2V mRNA levels were low at 0 h and did not change in response to hCG. cPLA2 and sPLA2V were detected by immunocytochemistry in granulosa cells of periovulatory follicles before and at all times after hCG administration. PLA2 activity was low in lysates of granulosa cells obtained 0-24 h after hCG and was elevated in granulosa cells obtained 36 h after hCG administration. A cPLA2-selective inhibitor decreased both PLA2 activity in monkey granulosa cell lysates and PGE2 accumulation in cultures of human granulosa-lutein cells. Conclusions: cPLA2 is primarily or exclusively responsible for the gonadotropin-stimulated mobilization of arachidonic acid necessary for PG production by primate periovulatory follicles.