TUMOR-NECROSIS-FACTOR-ALPHA INHIBITS FOLLICLE-STIMULATING HORMONE-INDUCED GRANULOSA-CELL ESTRADIOL SECRETION IN THE HUMAN - DEPENDENCE ON SIZE OF FOLLICLE

This study investigated the effects of tumour necrosis factor-alpha (T NF) on human granulosa cells taken from ovaries of 11 premenopausal wo men undergoing oophorectomy during the luteal phase of the cycle for r easons unrelated to ovarian pathology, Granulosa cells from follicles ranging from 5-10 mm diameter (small) and from >10-25 mm (large) were subjected to culture for 48 and 96 h, Granulosa cells were cultured wi th human FSH (1 ng/ml), testosterone (1 mu M) and human TNF (10 ng/ml) , each alone, and in various combinations. In granulosa cells of small follicles, FSH alone increased progesterone and cAMP accumulation and the conversion of testosterone to oestradiol, In granulosa cells of l arge follicles, FSH increased progesterone and cAMP accumulation but n ot the conversion of testosterone to oestradiol. Only in granulosa cel ls of small follicles did TNF significantly inhibit FSH-induced conver sion of testosterone to oestradiol but it was not apparent until the s econd 48 h of culture and concomitantly TNF did not alter the ability of FSH to stimulate progesterone and cAMP accumulation, In granulosa c ells of large follicles, TNF did not alter FSH-stimulated oestradiol, progesterone or cAMP accumulation, Interestingly, progesterone accumul ation in the presence of TNF and FSH was significantly greater in gran ulosa cells of large follicles than in granulosa cells of small follic les. The results indicate that TNF suppresses FSH-induced oestradiol s ecretion in granulosa cells from small follicles and this modulatory e ffect of TNF appears to be independent of decreases in progesterone an d cAMP, The potential physiological significance of these findings is that TNF may be a relevant cytokine in suppressing FSH-induced oestrad iol secretion and follicular growth during the luteal phase of the cyc le.