DIFFERENTIAL RESPONSES OF GRANULOSA-CELLS FROM SMALL AND LARGE FOLLICLES TO FOLLICLE-STIMULATING-HORMONE (FSH) DURING THE MENSTRUAL-CYCLE AND ACYCLICITY - EFFECTS OF TUMOR-NECROSIS-FACTOR-ALPHA

This study determined effects of follicle stimulating hormone (FSH) al one and in combination with tumour necrosis factor (TNF), on granulosa cells from small (5-10 mm diameter) and large (>10-25 mm) follicles d uring follicular and luteal phases of the cycle and during periods of acyclicity. Granulosa cells were collected from ovaries of premenopaus al women undergoing oophorectomy, The cells were cultured with human F SH (2 ng/ml) and testosterone (1 mu M) in the presence or absence of h uman TNF-alpha (20 ng/ml), Media were removed at 48 and 96 h after cul ture and progesterone, oestradiol and cAMP in media were measured by r adioimmunoassays, FSH stimulated the accumulation of oestradiol from g ranulosa cells of small follicles during the follicular and luteal pha ses but not during acyclicity; and TNF reduced oestradiol accumulation in the presence of FSH, Interestingly, in granulosa cells from small follicles, progesterone and cAMP secretion increased in response to FS H and neither was affected by TNF. Thus, TNF specifically inhibited th e conversion of testosterone to oestradiol in granulosa cells from sma ll follicles, FSH stimulated oestradiol production by granulosa cells of large follicles obtained only during the follicular phase of the cy cle and TNF inhibited the FSH-induced oestradiol secretion. Granulosa cells obtained from large follicles during the luteal phase and during acyclicity did not accumulate oestradiol in response to FSH, However, FSH increased progesterone and cAMP secretion by granulosa cells obta ined from large follicles during the follicular and luteal phases. Dur ing the luteal phase alone, TNF in combination with FSH increased prog esterone accumulation above that of FSH alone. FSH did not increase pr ogesterone, oestradiol or cAMP secretion by granulosa cells obtained f rom large follicles during acyclicity. Thus, FSH increases progesteron e, oestradiol and cAMP secretion by granulosa cells of small follicles during the follicular and luteal phases and TNF appears to inhibit FS H-induced oestradiol secretion specifically in those cells. In large f ollicles, FSH-stimulated granulosa cell secretion of oestradiol is lim ited to the follicular phase and this effect can be inhibited by TNF, In addition, when granulosa cells of large follicles do not increase o estradiol secretion in response to FSH, TNF stimulates progesterone se cretion.