Tumour necrosis factor-alpha inhibits follicle-stimulating hormone-induced granulosa cell oestradiol secretion in the human: dependence on size of follicle.

Abstract

This study investigated the effects of tumour necrosis factor-alpha (TNF) on human granulosa cells taken from ovaries of 11 premenopausal women undergoing oophorectomy during the luteal phase of the cycle for reasons 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 with human FSH (1 ng/ml), testosterone (1 microM) 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 large follicles, FSH increased progesterone and cAMP accumulation but not the conversion of testosterone to oestradiol. Only in granulosa cells of small follicles did TNF significantly inhibit FSH-induced conversion of testosterone to oestradiol but it was not apparent until the second 48 h of culture and concomitantly TNF did not alter the ability of FSH to stimulate progesterone and cAMP accumulation. In granulosa cells of large follicles, TNF did not alter FSH-stimulated oestradiol, progesterone or cAMP accumulation. Interestingly, progesterone accumulation in the presence of TNF and FSH was significantly greater in granulosa cells of large follicles than in granulosa cells of small follicles. The results indicate that TNF suppresses FSH-induced oestradiol secretion in granulosa cells from small follicles and this modulatory effect of TNF appears to be independent of decreases in progesterone and cAMP. The potential physiological significances of these findings is that TNF may be a relevant cytokine in suppressing FSH-induced oestradiol secretion and follicular growth during the luteal phase of the cycle.