TUMOR-NECROSIS-FACTOR-ALPHA (TNF-ALPHA) INHIBITS STEROIDOGENESIS OF BOVINE OVARIAN GRANULOSA AND THECAL CELLS IN-VITRO - INVOLVEMENT OF TNF-ALPHA RECEPTORS

The effect of recombinant bovine tumor necrosis factor-alpha (TNF-alph a) on steroidogenesis and numbers of bovine ovarian granulosa and thec al cells has been studied, and specific binding sites for I-125-TNF-al pha on ovarian cells have been determined. Granulosa cells have been e xamined from small (surface diameter 1-5 mm) follicles, whereas thecal cells from large (greater than or equal to 8 mm) follicles were utili zed, Increasing doses of TNF-alpha significantly attenuated insulin-an d IGF-I-induced estradiol production by granulosa cells from small fol licles, but had no effect on basal estradiol production. Moreover, TNF -alpha significantly attenuated insulin-and LH-induced androstenedione production by thecal cells from targe follicles, TNF-alpha had little or no effect on the numbers of granulosa and thecal cells in these sa me studies. Specific high-affinity, low-capacity binding of I-125-TNF- alpha was also demonstrable in granulosa and thecal cells. Thus, it ap pears that TNF-alpha inhibits insulin- and IGF-I-induced estradiol pro duction by granulosa cells and androstenedione production by thecal ce lls via TNF-alpha binding to its own receptor.