EFFECTS OF TUMOR-NECROSIS-FACTOR-ALPHA (TNF-ALPHA) ON OVULATION IN THE RAT OVARY

The effects of tumour necrosis factor alpha (TNF alpha) on ovulation rate, ovarian secretion of steroids, and on tissue concentrations of the ovulatory mediators plasminogen activator (PA) and prostaglandins were examined in rat ovaries perfused in vitro for 20 h. Unstimulated control ovaries did not ovulate whereas luteinizing hormone (LH; 100 ng mL(-1)) induced ovulations in all ovaries (2.6+/-0.7). TNF alpha (40 ng mL(-1)) induced ovulations in 3 of 5 ovaries (0.8+/-0.4). When TNF alpha was added concomitantly with LH, the LH-induced ovulation rate was increased four-fold (10.6+/-1.3). This effect was not seen when TNF alpha was added 5 h after LH (3.2+/-0.6). More progesterone was released when TNF alpha was combined with LH by comparison with LH alone. Tissue concentrations of prostaglandin F-2 alpha (PGF(2 alpha)) and PGE were increased by the addition of TNF alpha when compared with the control group, but did not exceed those observed in the LH group, when TNF alpha was combined with LH. PA activity in the tissue was unaffected by TNF alpha and the LH-induced increase in PA activity was inhibited when TNF alpha was combined with LH. The results demonstrate that the proinflammatory cytokine TNF alpha promotes ovulations in the rat ovary.