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催产素受体拮抗剂对假孕大鼠卵巢和子宫合成及释放前列腺素F2α的影响。

Effect of an oxytocin receptor antagonist on ovarian and uterine synthesis and release of prostaglandin F2 alpha in pseudopregnant rats.

作者信息

Motta A B, Franchi A M, Faletti A, Gimeno M F

机构信息

Centro de Estudios Farmacologicos y Botanicos (CEFYBO), Consejo Nacional de Investigaciones Cientificas y Tecnicas de la Republica Argentina (CONICET), Buenos Aires, Argentina.

出版信息

Prostaglandins Leukot Essent Fatty Acids. 1996 Feb;54(2):95-100. doi: 10.1016/s0952-3278(96)90065-4.

DOI:10.1016/s0952-3278(96)90065-4
PMID:8848436
Abstract

There is substantial experimental evidence suggesting that oxytocin has a role in luteolysis in ruminates. Endogenous pulses of uterine prostaglandin (PG) F2 alpha occur synchronously with pulses of oxytocin during luteolysis; leading us to propose a possible feedback loop between uterine PGF2 alpha and luteal oxytocin. In rates, the mechanism whereby oxytocin acts has not been well elucidated. In the present report, the effects of an oxytocin receptor antagonist in pseudopregnant rats were investigated. Pseudopregnancy was induced in immature female rats by gonadotrophin treatment; this resulted in the formation of corpus luteum that remained functional for 9 +/- 1 days. The pseudopregnant rats were assigned to one of the following four groups. In the first group the relationship between the release of ovarian and uterine PGF2 alpha was tested. We also studied the serum progesterone during the pseudopregnancy. We found that PGF2 alpha released into the incubation medium from ovaries of pseudopregnant rats increased (p < 0.05) and was maximal on day 9 of pseudopregnancy. This concentration remained high until day 10 of pseudopregnancy and then decreased. The PGF2 alpha released from the uterus to the incubation medium rose (p < 0.05) on day 8 of pseudopregnancy and reached the peak value on day 10. the serum progesterone was increased (p < 0.001) on day 2 pseudopregnancy and was greater on day 5 (p < 0.001). The second and third group received a specific oxytocin receptor antagonist (1-deamino-2-O-methyltyrosine) in two different concentrations (0.05 or 0.2 mumol/l before the peak of PG release. Both doses employed decreased (p < 0.001) the release into the incubating medium of PGF2 alpha from ovaries and uterus. Indeed, after the treatment, the progesterone levels were higher (p < 0.001) than control on day 10 of pseudopregnancy. In the fourth group, a potent inhibitor of cyclooxygenase activity was administered on day 8 of pseudopregnancy into the ovarian bursa. The serum progesterone levels increased (p < 0.01) compared to control suggesting a possible role of ovarian PG in the luteolytic phase of the corpus luteum regression. Thus, our findings show that oxytocin is luteolytic in pseudopregnant rats and this action is mediated by oxytocin receptors, as it was blocked by a specific oxytocin receptor antagonist.

摘要

有大量实验证据表明,催产素在反刍动物的黄体溶解过程中发挥作用。在黄体溶解期间,子宫前列腺素(PG)F2α的内源性脉冲与催产素脉冲同步出现;这使我们提出子宫PGF2α与黄体催产素之间可能存在反馈回路。在大鼠中,催产素发挥作用的机制尚未得到充分阐明。在本报告中,研究了催产素受体拮抗剂对假孕大鼠的影响。通过促性腺激素处理诱导未成熟雌性大鼠假孕;这导致黄体形成,其功能可持续9±1天。将假孕大鼠分为以下四组之一。在第一组中,测试了卵巢和子宫PGF2α释放之间的关系。我们还研究了假孕期间的血清孕酮。我们发现,从假孕大鼠卵巢释放到孵育培养基中的PGF2α增加(p<0.05),并在假孕第9天达到最大值。该浓度在假孕第10天之前一直保持较高水平,然后下降。从子宫释放到孵育培养基中的PGF2α在假孕第8天上升(p<0.05),并在第10天达到峰值。血清孕酮在假孕第2天增加(p<0.001),在第5天更高(p<0.001)。第二组和第三组在PG释放峰值前分别接受两种不同浓度(0.05或0.2μmol/l)的特异性催产素受体拮抗剂(1-脱氨基-2-O-甲基酪氨酸)。所使用的两种剂量均降低了(p<0.001)PGF2α从卵巢和子宫释放到孵育培养基中的量。实际上,治疗后,假孕第10天的孕酮水平高于对照组(p<0.001)。在第四组中,在假孕第8天向卵巢囊中注射一种有效的环氧化酶活性抑制剂。与对照组相比,血清孕酮水平升高(p<0.01),表明卵巢PG在黄体退化的黄体溶解期可能发挥作用。因此,我们的研究结果表明,催产素在假孕大鼠中具有黄体溶解作用,并且这种作用是由催产素受体介导的,因为它被特异性催产素受体拮抗剂所阻断。

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引用本文的文献

1
Opposing actions of prostaglandins and oxytocin determine the onset of murine labor.前列腺素和催产素的拮抗作用决定了小鼠分娩的开始。
Proc Natl Acad Sci U S A. 1998 Sep 29;95(20):11875-9. doi: 10.1073/pnas.95.20.11875.