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In Vitro Reporter Assays for Screening of Chemicals That Disrupt Androgen Signaling

机译:筛选可干扰雄激素信号的化学物质的体外记者测定

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摘要

Endocrine disruptive chemicals (EDCs) modulate hormone signaling and cause developmental and reproductive anomalies. Today, there is a global concern regarding endocrine disruption effects, particularly those mediated by the androgen receptor (AR). Androgen or male hormones are critical for the development and maintenance of male characteristics and numerous EDCs exist in the environment with the potential to disrupt androgen action. The threat is more during critical developmental windows when there is increased sensitivity to these compounds. Timely screening and detection of the EDCs is essential to minimize deleterious effects produced by these toxic chemicals. As a first line of screening, in vitro transcription assays are very useful due to their speed, convenience, and cost effectiveness. In this paper, recent in vitro reporter assays for detecting androgenic or antiandrogenic activity of EDCs have been reviewed. Two important cell systems used for this purpose, namely, the mammalian or yeast cell systems, have been discussed. Use of reporter genes such as bacterial luciferase (lux) and green fluorescent protein (gfp) has significantly improved speed and sensitivity of detection. Also, many of the current reporter assay systems can be used in a high throughput format allowing speedy evaluation of multiple potential EDCs at a lower price.
机译:内分泌破坏性化学物质(EDC)调节激素信号传导,并引起发育和生殖异常。如今,关于内分泌干扰作用,特别是由雄激素受体(AR)介导的内分泌干扰作用,已引起全球关注。雄激素或雄性激素对于男性特征的形成和维持至关重要,并且环境中存在许多可能破坏雄激素作用的EDC。当对这些化合物的敏感性增加时,在关键的发育窗口期间威胁更大。及时筛选和检测EDC对于将这些有毒化学物质产生的有害影响降至最低至关重要。作为筛选的第一线,体外转录分析由于其速度,便利性和成本效益而非常有用。在本文中,对用于检测EDC的雄激素或抗雄激素活性的最新体外报告基因检测方法进行了综述。已经讨论了用于该目的的两个重要的细胞系统,即哺乳动物或酵母细胞系统。使用报告基因(例如细菌荧光素酶(lux)和绿色荧光蛋白(gfp))显着提高了检测速度和灵敏度。同样,许多当前的报告检测系统可以以高通量格式使用,从而可以以较低的价格快速评估多个潜在的EDC。

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