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内分泌干扰生物标志物:增塑剂对类固醇一期和二期代谢影响的聚类分析

Biomarkers of endocrine disruption: cluster analysis of effects of plasticisers on Phase 1 and Phase 2 metabolism of steroids.

作者信息

Waring R H, Ramsden D B, Jarratt P D B, Harris R M

机构信息

School of Biosciences, University of Birmingham, Birmingham, UK.

出版信息

Int J Androl. 2012 Jun;35(3):415-23. doi: 10.1111/j.1365-2605.2012.01248.x. Epub 2012 Feb 28.

DOI:10.1111/j.1365-2605.2012.01248.x
PMID:22372686
Abstract

Although some endocrine disruptors (EDs) act at steroid receptors, it is now apparent that compounds may have ED potential if they alter steroid synthesis or metabolism, particularly if they affect Phase 1 or Phase 2 pathways. In the ENDOMET project (EU-funded 5th Framework programme), 23 different assays were used on a wide range of EDs. Cluster analysis of the matrix results enabled identification of four integrated test systems that can be used to pinpoint compounds that are able to alter steroid metabolism or function. Critical pathways were shown to include oestrogen synthesis and sulphonation, synthesis of sulphate/PAPS and thyroid hormone regulation so that the activity profiles of some Phase 1 and Phase 2 reactions can be used as biomarkers for detection of compounds with ED potential.

摘要

尽管一些内分泌干扰物(EDs)作用于类固醇受体,但现在很明显,如果化合物改变类固醇的合成或代谢,特别是影响Ⅰ相或Ⅱ相途径,那么它们可能具有内分泌干扰潜力。在ENDOMET项目(欧盟资助的第五框架计划)中,对多种内分泌干扰物进行了23种不同的检测。对基质结果进行聚类分析,确定了四个综合测试系统,可用于精准识别能够改变类固醇代谢或功能的化合物。关键途径包括雌激素合成与磺化、硫酸盐/3'-磷酸腺苷-5'-磷酸硫酸(PAPS)合成以及甲状腺激素调节,因此一些Ⅰ相和Ⅱ相反应的活性谱可作为检测具有内分泌干扰潜力化合物的生物标志物。

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