Tumor necrosis factor-alpha (TNF-alpha) inhibits steroidogenesis of bovine ovarian granulosa and thecal cells in vitro. Involvement of TNF-alpha receptors

Abstract

The effect of recombinant bovine tumor necrosis factor-alpha (TNF-alpha) on steroidogenesis and numbers of bovine ovarian granulosa and thecal cells has been studied, and specific binding sites for 125I-TNF-alpha on ovarian cells have been determined. Granulosa cells have been examined from small (surface diameter 1-5 mm) follicles, whereas thecal cells from large (> or = 8 mm) follicles were utilized. Increasing doses of TNF-alpha significantly attenuated insulin- and IGF-I-induced estradiol production by granulosa cells from small follicles, but had no effect on basal estradiol production. Moreover, TNF-alpha significantly attenuated insulin- and LH-induced androstenedione production by thecal cells from large follicles. TNF-alpha had little or no effect on the numbers of granulosa and thecal cells in these same studies. Specific high-affinity, low-capacity binding of 125I-TNF-alpha was also demonstrable in granulosa and thecal cells. Thus, it appears that TNF-alpha inhibits insulin- and IGF-I-induced estradiol production by granulosa cells and androstenedione production by thecal cells via TNF-alpha binding to its own receptor.