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 r ate, ovarian secretion of steroids, and on tissue concentrations of th e ovulatory mediators plasminogen activator (PA) and prostaglandins we re examined in rat ovaries perfused in vitro for 20 h. Unstimulated co ntrol ovaries did not ovulate whereas luteinizing hormone (LH; 100 ng mL(-1)) induced ovulations in all ovaries (2.6+/-0.7). TNF alpha (40 n g mL(-1)) induced ovulations in 3 of 5 ovaries (0.8+/-0.4). When TNF a lpha was added concomitantly with LH, the LH-induced ovulation rate wa s 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 releas ed when TNF alpha was combined with LH by comparison with LH alone. Ti ssue concentrations of prostaglandin F-2 alpha (PGF(2 alpha)) and PGE were increased by the addition of TNF alpha when compared with the con trol group, but did not exceed those observed in the LH group, when TN F 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 ova ry.