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外源性雌激素:作用机制与检测方法

Xenoestrogens: mechanisms of action and detection methods.

作者信息

Mueller Stefan O

机构信息

Molecular Toxicology, Institute of Toxicology, Merck KGaA, PO Box, 64271 Darmstadt, Germany.

出版信息

Anal Bioanal Chem. 2004 Feb;378(3):582-7. doi: 10.1007/s00216-003-2238-x. Epub 2003 Oct 16.

Abstract

Estrogenic compounds exert pleiotropic effects in wildlife and humans, and endogenous estrogens, like 17 beta-estradiol, regulate growth and development of their target tissues. Environmental, industrial, or naturally occurring chemicals that possess estrogenic and/or antiestrogenic activities are termed xenoestrogens and may interfere with endocrine systems. These xenoestrogens are therefore defined as endocrine-active or endocrine-disrupting compounds. The estrogen receptor (ER) is the major regulatory unit within the estrogen-signaling pathway and the molecular mechanisms of estrogen and ER actions are described briefly. Based on the mechanism of ER action, in vitro test systems are described that can be employed for screening but also for the elucidation of mechanisms of action of (anti)estrogenic compounds. How screening assays and mechanistic studies can aid in human risk assessment for potential endocrine-active compounds is discussed also.

摘要

雌激素化合物在野生动物和人类中发挥着多效性作用,内源性雌激素,如17β-雌二醇,调节其靶组织的生长和发育。具有雌激素和/或抗雌激素活性的环境、工业或天然存在的化学物质被称为外源性雌激素,可能会干扰内分泌系统。因此,这些外源性雌激素被定义为内分泌活性或内分泌干扰化合物。雌激素受体(ER)是雌激素信号通路中的主要调节单元,本文简要描述了雌激素和ER作用的分子机制。基于ER作用机制,介绍了可用于筛选以及阐明(抗)雌激素化合物作用机制的体外测试系统。本文还讨论了筛选试验和机制研究如何有助于对潜在内分泌活性化合物进行人类风险评估。

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