Lymphocytes stimulate progesterone production by cultured human granulosa luteal cells

After follicular rupture, massive invasion of blood vessels with neovascularization of the developing corpus luteum takes place, providing many chances for direct contact of luteal cells with resident and migrating immune cells. We studied the effects of peripheral blood lymphocytes on progesterone production by human granulosa luteal cells isolated from women undergoing in vitro fertilization. During 6 days of culture, progesterone production by granulosa luteal cells was significantly increased when they were cultured together with autologous or allogenic peripheral blood lymphocytes. This stimulatory effect was also observed on the addition of medium conditioned with peripheral blood lymphocytes and was synergistic with gonadotropin stimulation. The activity was present in the fraction retained by ultrafiltration with a 30,000 molecular weight cutoff filter and was preserved after heating at 56 degrees C for 30 minutes but disappeared after heating at 70 degrees C for 15 minutes. These findings suggest that lymphocytes infiltrating the corpus luteum during early luteinization can stimulate the function of human granulosa luteal cells through the action of some protein-like humoral factor(s) of higher molecular weight than that of previously identified lymphokines and indicate a possible paracrinologic regulatory role for lymphocytes in ovarian function.