Differential estrogenic actions of endocrine-disrupting chemicals bisphenol A, bisphenol AF, and zearalenone through estrogen receptor α and β in vitro.
Differential estrogenic actions of endocrine-disrupting chemicals bisphenol A, bisphenol AF, and zearalenone through estrogen receptor α and β in vitro.
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DOI：
10.1289/ehp.1104689
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发表时间：
2012-07
影响因子：
10.4
通讯作者：
Korach KS
中科院分区：
文献类型：
--
作者：
Li Y;Burns KA;Arao Y;Luh CJ;Korach KS
背景：环境中广泛存在内分泌干扰物质（EDCs）。雌激素样活性归因于EDCs，如双酚A （BPA）、双酚AF （BPAF）和玉米烯酮（Zea），但其作用机制和影响的多样性尚不清楚。目的：采用体外模型研究BPA、BPAF和Zea对雌激素受体(ER) α和ERβ的作用机制。方法：采用石川细胞系、HeLa细胞系和HepG2细胞系3种细胞类型，研究BPA、BPAF和Zea对ERα和ERβ的雌激素促进因子活性。石川/ERα稳定细胞用于测定雌激素反应元件（ERE）介导的靶基因表达变化或快速作用介导的效应。结果：三种EDCs均表现出较强的ERα受体激动剂活性，且呈剂量依赖性。在较低浓度下，BPA在Ishikawa细胞中可作为ERα拮抗剂，BPAF在HeLa细胞中可作为ERβ拮抗剂，而Zea仅是ERα的部分拮抗剂。BPA和BPAF通过ERα的AF-2功能激活ere，而Zea通过AF-1和AF-2功能激活。BPA、BPAF和Zea可激活内源性ERα靶基因和通过p44/42 MAPK途径的快速信号传导。结论：BPA和BPAF可作为ERα和ERβ的细胞类型特异性激动剂（≥10 nM）或拮抗剂（≤10 nM）发挥EDCs的功能。玉米具有较强的雌激素活性，可激活ERα的AF-1和AF-2功能。此外，这三种化合物都能诱导ERα的快速动作介导反应。
Background: Endocrine-disrupting chemicals (EDCs) are widely found in the environment. Estrogen-like activity is attributed to EDCs, such as bisphenol A (BPA), bisphenol AF (BPAF), and zearalenone (Zea), but mechanisms of action and diversity of effects are poorly understood. Objectives: We used in vitro models to evaluate the mechanistic actions of BPA, BPAF, and Zea on estrogen receptor (ER) α and ERβ. Methods: We used three human cell lines (Ishikawa, HeLa, and HepG2) representing three cell types to evaluate the estrogen promoter activity of BPA, BPAF, and Zea on ERα and ERβ. Ishikawa/ERα stable cells were used to determine changes in estrogen response element (ERE)-mediated target gene expression or rapid action-mediated effects. Results: The three EDCs showed strong estrogenic activity as agonists for ERα in a dose-dependent manner. At lower concentrations, BPA acted as an antagonist for ERα in Ishikawa cells and BPAF acted as an antagonist for ERβ in HeLa cells, whereas Zea was only a partial antagonist for ERα. ERE-mediated activation by BPA and BPAF was via the AF-2 function of ERα, but Zea activated via both the AF-1 and AF-2 functions. Endogenous ERα target genes and rapid signaling via the p44/42 MAPK pathway were activated by BPA, BPAF, and Zea. Conclusion: BPA and BPAF can function as EDCs by acting as cell type–specific agonists (≥ 10 nM) or antagonists (≤ 10 nM) for ERα and ERβ. Zea had strong estrogenic activity and activated both the AF-1 and AF-2 functions of ERα. In addition, all three compounds induced the rapid action-mediated response for ERα.
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影响因子：
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