DIFFERENTIAL REGULATION OF PROGESTERONE AND ESTRADIOL PRODUCTION BY MOUSE CUMULUS AND MURAL GRANULOSA-CELLS BY A FACTOR(S) SECRETED BY THE OOCYTE

Mouse oocytes secrete a factor(s) that inhibits progesterone and enhan ces estradiol production by cumulus granulosa cells. The purpose of th is study was to investigate the mechanisms by which the production of these steroids is modulated. Mouse oocyte-cumulus cell complexes (inta ct) and complexes from which the oocytes were removed microsurgically (oocytectomized; OOX) were cultured for up to 48 h in the presence of FSH (150 ng/ml) and testosterone (5 x 10(-7) M). For these experiments , all cells were obtained from antral follicles of 24- to 26-day-old m ice primed with eCG. Intact complexes produced primarily estradiol, wi th significant accumulation occurring between 24 and 48 h. In contrast , OOX complexes produced little estradiol but, starting at 18 h of cul ture, released significantly more progesterone than did intact complex es. Progesterone accumulation in cocultures of denuded oocytes with ei ther OOX complexes or monolayers of mural granulosa cells was signific antly reduced compared to that with OOX complexes or mural granulosa c ells cultured alone. If dibutyryl cAMP replaced FSH in the cocultures, similar results were obtained, suggesting that the oocyte-secreted st eroid-regulating factor acts downstream of the generation of cAMP to i nhibit progesterone production. Since estradiol can inhibit progestero ne production by granulosa cells, we investigated the possibility that the increased progesterone released by OOX complexes was secondary to the lower estradiol production. intact complexes cultured in the pres ence of the nonaromatizable androgen, 5 alpha-dihydrotestosterone, or steroidal (4-hydroxyandrostenedione) or non-steroidal (CGS 16949A) aro matase inhibitors produced little estradiol; however, progesterone pro duction by these complexes was no different from that of estradiol-pro ducing intact complexes. These results suggest that the steroid-regula ting factor(s) secreted by oocytes acts to regulate granulosa cell pro duction of estradiol and progesterone by independent mechanisms.