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

Comparison of inhibitory actions of indomethacin and epostane on ovulation in rats.
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DOI:
10.1152/ajpendo.1991.260.2.e170
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发表时间:
1991-02
期刊:
The American journal of physiology
影响因子:
--
通讯作者:
N. Tanaka;L. Espey;T. Kawano;H. Okamura
N. Tanaka;L. Espey;T. Kawano;H. Okamura
中科院分区:
其他
文献类型:
--
作者:
N. Tanaka;L. Espey;T. Kawano;H. Okamura

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吲哚美辛,一种从花生四烯酸产生前列腺素(PG)的环氧合酶抑制剂,和2 α,4 α,7- 4,5-环氧-17-羟基-4,17-二甲基-3-氧代雄甾烷-2-腈(epostane),一种从去甲烯醇酮产生孕酮的3 β-羟基类固醇脱氢酶抑制剂,都是有效的排卵抑制剂。本报告比较了这两种抑制剂对25日龄未成熟Wistar大鼠排卵期间卵巢5-、12-和15-羟基二十碳四烯酸甲酯(HETEs)、前列腺素E2(PGE)、前列腺素F2 α(PGF)、孕酮、17 α-羟孕酮、17 β-雌二醇、4-雄烯-3,17-二酮和睾酮水平的剂量依赖性影响。排卵过程由10 IU的人绒毛膜促性腺激素(hCG)启动。吲哚美辛在hCG后3 h给药,剂量范围为0.0316 - 10.0 mg/大鼠。0.1 mg/大鼠的剂量是显著降低排卵率的最低剂量,对照水平为70.5 +/- 5.8个卵子/大鼠。这个剂量也减少了15-HETE,但不是5-HETE,12-HETE,或类固醇。PGE和PGF被更低剂量的吲哚美辛(0.0316 mg/只)强烈抑制,但该剂量不影响排卵率。在hCG后3 h给予Epostane,剂量范围为0.1 - 5.0 mg/大鼠。1.0 mg/大鼠的剂量是显著抑制排卵的最低剂量。该剂量也降低了卵巢中15-HETE和孕酮的水平,但不降低5-HETE、12-HETE、PGE、PGF或其他类固醇的水平。结果表明,排卵率与卵巢15-HETE水平密切相关。
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.