Comparison of inhibitory actions of indomethacin and epostane on ovulation in rats.
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.
Tanaka
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Department of Biology, Trinity University, San Antonio, Texas 78212.
Espey
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LL
Kawano
T
T
Okamura
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H
D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D019326:17-alpha-Hydroxyprogesterone; D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine / Q000494:pharmacology; D000735:Androstenedione / Q000378:metabolism; D000737:Androstenols / Q000494:pharmacology*; D000818:Animals; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D004958:Estradiol / Q000378:metabolism; D005260:Female; D006893:Hydroxyeicosatetraenoic Acids / Q000378:metabolism; D006908:Hydroxyprogesterones / Q000378:metabolism; D007213:Indomethacin / Q000494:pharmacology*; D009637:Masoprocol / Q000494:pharmacology; D010060:Ovulation / Q000187:drug effects*; D010062:Ovulation Induction; D011374:Progesterone / Q000378:metabolism; D011458:Prostaglandins E / Q000378:metabolism; D011460:Prostaglandins F / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013256:Steroids / Q000378:metabolism*; D013739:Testosterone / Q000378:metabolism
D000737:Androstenols; D006063:Chorionic Gonadotropin; D006893:Hydroxyeicosatetraenoic Acids; D006908:Hydroxyprogesterones; D011458:Prostaglandins E; D011460:Prostaglandins F; D013256:Steroids; D013739:Testosterone; D000735:Androstenedione; C022022:5-hydroxy-6,8,11,14-eicosatetraenoic acid; D011374:Progesterone; D004958:Estradiol; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; C046855:epostane; D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; D019326:17-alpha-Hydroxyprogesterone; C025984:15-hydroxy-5,8,11,13-eicosatetraenoic acid; D009637:Masoprocol; D007213:Indomethacin