Dissociation of ovulatory and steroidogenic actions of luteinizing hormone in rabbits with indomethacin, an inhibitor of prostaglandin biosynthesis

Abstract

The possible involvement of prostaglandins as mediators of ovarian responses to luteinizing hormone (LH) has been investigated in in vivo studies with the aid of indomethacin (1-[p-chlorobenzoyl]-5-methoxy-2-methylindole-3-acetic acid), an inhibitor of prostaglandin biosynthesis. LH (50 μg NIH-LH-B7) was injected i.v. 1 2 hour after i.v. injection of either indomethacin (20 – 40 mg/Kg) or phosphate buffer vehicle. Mean levels of progesterone and 20α-hydroxypregn-4-en-3-one (20α-OH-P) observed in peripheral plasma obtained by cardiac puncture 1 hour after LH were increased by 5.35 ± 1.48 and 26.0 ± 11.6 ng/ml respectively in phosphate buffer-treated controls, and by 5.60 ± 4.47 and 100.6 ± 37.1 ng/ml respectively in indomethacin-treated rabbits. The apparently greater increase in 20α-OH-P in indomethacin-treated rabbits could be attributed almost entirely to the larger amounts of interstitial tissue in the latter animals, as indicated by essential disappearance of this difference when covariance analyses were performed to correct for this difference in ovarian interstitial tissue weight. None of 12 indomethacin-treated, and 10 of 11 vehicle-treated control rabbits ovulated in response to this dosage of LH, as determined by flushing of oviducts to recover ova, and by gross examination of ovaries 1 or 3 days after LH treatment. Indomethacin did not prevent luteinization of follicles in LH-treated rabbits, as determined by gross and histologic examination of ovaries 8 days after treatment. These findings argue against a role of prostaglandins as mediators of the acute steroidogenic and luteinizing actions of LH in the rabbit ovary, but suggest an involvement in the process of ovulation.