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DOI | 10.1289/EHP396 |
Differential Activation of a Mouse Estrogen Receptor beta Isoform (mER beta 2) with Endocrine-Disrupting Chemicals (EDCs) | |
Donoghue, Lauren J.; Neufeld, Thomas I.; Li, Yin; Arao, Yukitomo; Coons, Laurel A.; Korach, Kenneth S. | |
2017-04-01 | |
发表期刊 | ENVIRONMENTAL HEALTH PERSPECTIVES
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ISSN | 0091-6765 |
EISSN | 1552-9924 |
出版年 | 2017 |
卷号 | 125期号:4 |
文章类型 | Article |
语种 | 英语 |
国家 | USA |
英文摘要 | Background: Endocrine-disrupting chemicals (EDCs) are suspected of altering estrogenic signaling through estrogen receptor (ER) alpha or beta (mER beta 1 in mice). Several EDC effects have been reported in animal studies and extrapolated to human studies. Unlike humans, rodents express a novel isoform of ER beta (mER beta 2) with a modified ligand-binding domain sequence. EDC activity through this isoform remains uncharacterized. Objectives: We identified the expression pattern of mER beta 2 in mouse tissues and assessed the estrogenic activity of EDCs through mER beta 2. Methods: mER beta 2 mRNA expression was measured in mouse tissues. HepG2 cells were used to assess the transactivation activity of mER beta isoforms with EDCs and ER co-activators. 293A cells transiently transfected with mER isoforms were used to detect EDC-mediated changes in endogenous ER target gene expression. Results: Expression of mER beta 2 mRNA was detected in mouse reproductive tissues (ovary, testis, and prostate) and lung and colon tissues from both female and male mice. Five (E2, DES, DPN, BPAF, Coum, 1-BP) of 16 compounds tested by reporter assay had estrogenic activity through mER beta 2. mER beta 2 had a compound-specific negative effect on ER beta/ligand-mediated activity and ER target genes when co-expressed with mER beta 1. mER beta 2 recruited coactivators SRC2 or SRC3 in the presence of EDCs, but showed less recruitment than mER beta 1. Conclusion: mER beta 2 showed weaker estrogenic activity than mER beta 1 in our in vitro system, and can dampen mER beta 1 activity. In vivo models of EDC activity and ER-mediated toxicity should consider the role of mER beta 2, as rodent tissue responses involving mER beta 2 may not be reproduced in human biology. |
领域 | 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000397904400025 |
WOS关键词 | BISPHENOL-A ; IN-VITRO ; ER-BETA ; MOLECULAR-MECHANISMS ; COREGULATORS ; ALPHA ; EXPOSURE ; IDENTIFICATION ; PATHOLOGY ; DISEASE |
WOS类目 | Environmental Sciences ; Public, Environmental & Occupational Health ; Toxicology |
WOS研究方向 | Environmental Sciences & Ecology ; Public, Environmental & Occupational Health ; Toxicology |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/22725 |
专题 | 资源环境科学 |
作者单位 | NIEHS, Receptor Biol Sect, Reprod & Dev Biol Lab, Div Intramural Res,NIH,Dept Hlth & Human Serv, Res Triangle Pk, NC USA |
推荐引用方式 GB/T 7714 | Donoghue, Lauren J.,Neufeld, Thomas I.,Li, Yin,et al. Differential Activation of a Mouse Estrogen Receptor beta Isoform (mER beta 2) with Endocrine-Disrupting Chemicals (EDCs)[J]. ENVIRONMENTAL HEALTH PERSPECTIVES,2017,125(4). |
APA | Donoghue, Lauren J.,Neufeld, Thomas I.,Li, Yin,Arao, Yukitomo,Coons, Laurel A.,&Korach, Kenneth S..(2017).Differential Activation of a Mouse Estrogen Receptor beta Isoform (mER beta 2) with Endocrine-Disrupting Chemicals (EDCs).ENVIRONMENTAL HEALTH PERSPECTIVES,125(4). |
MLA | Donoghue, Lauren J.,et al."Differential Activation of a Mouse Estrogen Receptor beta Isoform (mER beta 2) with Endocrine-Disrupting Chemicals (EDCs)".ENVIRONMENTAL HEALTH PERSPECTIVES 125.4(2017). |
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