急性管理3 beta-hydroxysteroid脱氢酶抑制剂在midluteal猕猴月经周期的阶段:自分泌的证据规定的灵长类动物黄体孕激素。

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达菲DM,赫斯DL,史都华牌RL

急性管理3 beta-hydroxysteroid脱氢酶抑制剂在midluteal猕猴月经周期的阶段:自分泌的证据规定的灵长类动物黄体孕激素。

中国性金属底座。1994年12月,79 (6):1587 - 94。

PubMed ID

7989460 (在PubMed

]

文摘

Colocalization孕激素受体和3 beta-hydroxysteroid脱氢酶(3 beta HSD),孕酮生物合成的关键酶,在猕猴黄体细胞表明孕激素有自分泌在灵长类动物黄体功能的调节作用。为了验证这个假设,我们trilostane管理,3βHSD抑制剂,在midluteal恒河猴自发月经周期迅速、可逆阶段减少孕酮生产。动物收到trilostane(600毫克/剂量;治疗组;n = 5)或车辆(对照组;n = 4)口头天黄体期的6 - 7。Trilostane显著(P < 0.05),孕烯醇酮水平升高1 h内治疗相比vehicle-treated动物;经过一天的治疗,意味着孕烯醇酮水平(173 nmol / L)是86倍大于控制价值。孕烯醇酮水平下降后停止药物管理局并成为区别控制水平13天。Trilostane显著降低血清孕激素水平在3 h的初始管理水平(P < 0.01),仍接近基线(1.0 nmol / L)在治疗的2天。 Progesterone levels also remained low after cessation of trilostane treatment in four of five monkeys, and trilostane-treated animals experienced a shorter luteal phase than vehicle-treated animals (7.8 +/- 0.2 vs. 16 +/- 1 days; P < 0.01). Histological analysis (n = 3/group) revealed indexes of premature structural luteolysis by 4 days after the onset of trilostane administration. Exposure to trilostane had no effect on the percentage of luteal cells expressing progesterone receptors, as determined by immunocytochemistry. Serum LH levels were not different between treatment and control groups throughout the experimental period. As trilostane dramatically reduced serum progesterone and induced premature menses without major concurrent alteration in serum cortisol, we conclude that trilostane ios an effective, rapidly acting inhibitor of 3 beta HSD in the macaque corpus luteum during the midluteal phase of the menstrual cycle. Progesterone production did not typically resume after cessation of trilostane treatment despite continuing gonadotropin support luteolysis. Thus, progesterone or a related metabolite may be required to maintain the function and structural integrity of the primate corpus luteum during the normal menstrual cycle.

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药物靶点

药物	目标	类	生物	药理作用	行动
Trilostane	3 beta-hydroxysteroid脱氢酶/δ5 - - > 4-isomerase 1型	蛋白质	人类	是的	抑制剂	细节
Trilostane	3 beta-hydroxysteroid脱氢酶/δ5 - - > 4-isomerase 2型	蛋白质	人类	是的	抑制剂	细节