Differential responses of granulosa cells from small and large follicles to follicle stimulating hormone (FSH) during the menstrual cycle and acyclicity: effects of tumour necrosis factor-alpha

This study determined effects of follicle stimulating hormone (FSH) aloneand in combination with tumour necrosis factor (TNF), on granulosa cellsfrom small (5-10 mm diameter) and large (>10-25 mm) follicles duringfollicular and luteal phases of the cycle and during periods of acyclicity.Granulosa cells were collected from ovaries of premenopausal womenundergoing oophorectomy. The cells were cultured with human FSH (2 ng/ml)and testosterone (1 microM) in the presence or absence of human TNF-alpha(20 ng/ml). Media were removed at 48 and 96 h after culture andprogesterone, oestradiol and cAMP in media were measured byradioimmunoassays. FSH stimulated the accumulation of oestradiol fromgranulosa cells of small follicles during the follicular and luteal phasesbut not during acyclicity; and TNF reduced oestradiol accumulation in thepresence of FSH. Interestingly, in granulosa cells from small follicles,progesterone and cAMP secretion increased in response to FSH and neitherwas affected by TNF. Thus, TNF specifically inhibited the conversion oftestosterone to oestradiol in granulosa cells from small follicles. FSHstimulated oestradiol production by granulosa cells of large folliclesobtained only during the follicular phase of the cycle and TNF inhibitedthe FSH-induced oestradiol secretion. Granulosa cells obtained from largefollicles during the luteal phase and during acyclicity did not accumulateoestradiol in response to FSH. However, FSH increased progesterone and cAMPsecretion by granulosa cells obtained from large follicles during thefollicular and luteal phases. During the luteal phase alone, TNF incombination with FSH increased progesterone accumulation above that of FSHalone. FSH did not increase progesterone, oestradiol or cAMP secretion bygranulosa cells obtained from large follicles during acyclicity. Thus, FSHincreases progesterone, oestradiol and cAMP secretion by granulosa cells ofsmall follicles during the follicular and luteal phases and TNF appears toinhibit FSH-induced oestradiol secretion specifically in those cells. Inlarge follicles, FSH- stimulated granulosa cell secretion of oestradiol islimited to the follicular phase and this effect can be inhibited by TNF. Inaddition, when granulosa cells of large follicles do not increaseoestradiol secretion in response to FSH, TNF stimulates progesteronesecretion.