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The methoxychlor metabolite, HPTE, inhibits rat luteal cell progesterone production.

机译:甲氧基氯代谢物HPTE抑制大鼠黄体细胞孕酮的产生。

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The methoxychlor metabolite, HPTE, was shown to inhibit P450-cholesterol side-chain cleavage (P450scc) activity resulting in decreased progesterone production by cultured ovarian follicular cells in previous studies. It is not known whether HPTE has any effect on progesterone formation by the corpus luteum. RESULTS: Exposure to 100 nM HPTE reduced progesterone production by luteal cells with progressive declines to <22% of control at 500 nM HPTE. Similarly, HPTE progressively inhibited progesterone formation and P450scc catalytic activity of hCG- or 8 Br-cAMP-stimulated luteal cells. However, HPTE did not alter mRNA and protein levels of P450scc. Compounds acting as estrogen (17 beta-estradiol, bisphenol-A or octylphenol), antiestrogen (ICI) or antiandrogen (monobutyl phthalate, flutamide or M-2) added alone to luteal cells did not mimic the action of HPTE on progesterone and P450scc activity. These results suggest that HPTE directly inhibits P450scc catalytic activity resulting in reduced progesterone formation, and this action was not mediated through estrogen or androgen receptors.
机译:在以前的研究中,甲氧基氯代谢产物HPTE可以抑制P450胆固醇侧链裂解(P450scc)活性,从而导致培养的卵泡细胞减少孕酮生成。尚不清楚HPTE是否对黄体形成孕激素有任何影响。结果:暴露于100 nM HPTE降低了黄体细胞的孕激素生成,在500 nM HPTE时逐渐降低至对照的<22%。同样,HPTE逐渐抑制hCG或8 Br-cAMP刺激的黄体细胞的孕酮形成和P450scc催化活性。但是,HPTE不会改变P450scc的mRNA和蛋白质水平。单独添加到黄体细胞中的雌激素(17β-雌二醇,双酚-A或辛基酚),抗雌激素(ICI)或抗雄激素(邻苯二甲酸单丁酯,氟他胺或M-2)的化合物不能模仿HPTE对孕酮和P450scc活性的作用。 。这些结果表明,HPTE直接抑制P450scc的催化活性,导致孕酮形成减少,并且该作用未通过雌激素或雄激素受体介导。

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