Dual effects of phytoestrogens result in u-shaped dose-response curves.
Dual effects of phytoestrogens result in u-shaped dose-response curves.
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DOI：
10.1289/ehp.02110743
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发表时间：
2002-08
影响因子：
10.4
通讯作者：
Leffers H
中科院分区：
文献类型：
--
作者：
Almstrup K;Fernández MF;Petersen JH;Olea N;Skakkebaek NE;Leffers H
内分泌干扰物可以影响内分泌系统，而不直接与受体相互作用，例如，通过干扰类固醇激素的合成或代谢。将睾酮转化为17 β-雌二醇的芳香酶是一个可能的靶点。在本文中，我们描述了一种测定，同时检测芳香化酶抑制和雌激素。其原理与其他MCF-7雌激素活性测定法相似，但添加了固定量的睾酮。MCF-7细胞中的内源性芳香酶活性将一些睾酮转化为17 β-雌二醇，这通过定量雌激素诱导的pS2 mRNA表达水平的差异来测定。潜在的芳香酶抑制剂可以通过暴露于睾酮和测试化合物后pS2 mRNA表达水平的剂量依赖性降低来鉴定。使用这种方法，我们已经研究了几种化合物，包括合成化学品和植物雌激素，芳香酶抑制。植物雌激素，除了染料木黄酮，在低浓度（< 1 μ M）时是芳香酶抑制剂，但在高浓度（大于或等于1 μ M）时是雌激素，导致U形剂量反应曲线。测试的合成化学品都不是芳香酶抑制剂。低剂量的芳香化酶抑制区分植物雌激素从其他雌激素化合物，并可能部分解释有关植物雌激素的抗雌激素特性的报告。芳香酶抑制可能在植物雌激素对乳腺癌的保护作用中发挥重要作用。
Endocrine disruptors can affect the endocrine system without directly interacting with receptors, for example, by interfering with the synthesis or metabolism of steroid hormones. The aromatase that converts testosterone to 17beta-estradiol is a possible target. In this paper we describe an assay that simultaneously detects aromatase inhibition and estrogenicity. The principle is similar to that of other MCF-7 estrogenicity assays, but with a fixed amount of testosterone added. The endogenous aromatase activity in MCF-7 cells converts some of the testosterone to 17beta-estradiol, which is assayed by quantifying differences in the expression level of the estrogen-induced pS2 mRNA. Potential aromatase inhibitors can be identified by a dose-dependent reduction in the pS2 mRNA expression level after exposure to testosterone and the test compound. Using this assay, we have investigated several compounds, including synthetic chemicals and phytoestrogens, for aromatase inhibition. The phytoestrogens, except genistein, were aromatase inhibitors at low concentrations (< 1 micro M) but estrogenic at higher concentrations (greater than or equal to 1 micro M), resulting in U-shaped dose-response curves. None of the tested synthetic chemicals were aromatase inhibitors. The low-dose aromatase inhibition distinguished phytoestrogens from other estrogenic compounds and may partly explain reports about antiestrogenic properties of phytoestrogens. Aromatase inhibition may play an important role in the protective effects of phytoestrogens against breast cancer.
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影响因子：
3.5
作者：
GRAY, SA;MANNAN, MA;OSHAUGHNESSY, PJ
通讯作者：
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通讯作者：
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作者：
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