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Am J Physiol Endocrinol Metab 260: E170-E174, 1991;
0193-1849/91 $5.00
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AJP - Endocrinology and Metabolism, Vol 260, Issue 2 E170-E174, Copyright © 1991 by American Physiological Society

ARTICLES

Comparison of inhibitory actions of indomethacin and epostane on ovulation in rats

N. Tanaka, L. L. Espey, T. Kawano and H. Okamura
Department of Biology, Trinity University, San Antonio, Texas 78212.

Indomethacin, an inhibitor of cyclooxygenase that generates prostaglandins (PGs) from arachidonic acid, and 2 alpha,4 alpha,7-4,5-epoxy-17-hydroxy-4,17-dimethyl-3-oxoandrostane- 2-carbonitrile (epostane), an inhibitor of 3 beta-hydroxysteroid dehydrogenase that generates progesterone from pregnenolone, are both potent inhibitors of ovulation. This report compares the dose-dependent effects of these two inhibitors on ovarian levels of 5-, 12-, and 15-hydroxyeicosatetraenoic acid methyl ester (HETEs), prostaglandin E2 (PGE), prostaglandin F2 alpha (PGF), progesterone, 17 alpha-hydroxyprogesterone, 17 beta-estradiol, 4-androstene-3,17-dione, and testosterone during ovulation in 25-day-old immature Wistar rats. The ovulatory process was initiated by 10 IU of human chorionic gonadotropin (hCG). Indomethacin was given at 3 h after hCG in doses ranging from 0.0316 to 10.0 mg/rat. A dose of 0.1 mg/rat was the lowest dose to significantly reduce the ovulation rate from the control level of 70.5 +/- 5.8 ova/rat. This dose also reduced 15-HETE, but not 5-HETE, 12-HETE, or the steroids. PGE and PGF were strongly inhibited by an even lower dose of indomethacin (0.0316 mg/rat), but this dose did not affect the ovulation rate. Epostane was given at 3 h after hCG in doses ranging from 0.1 to 5.0 mg/rat. A dose of 1.0 mg/rat was the lowest dose to significantly inhibit ovulation. This dose also reduced the ovarian levels of 15-HETE and progesterone but not 5-HETE, 12-HETE, PGE, PGF, or the other steroids. The results indicate that the ovulation rate is most closely correlated to ovarian 15-HETE levels.


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