Low concentrations of bisphenol a suppress thyroid hormone receptor transcription through a nongenomic mechanism

CORC > 生态环境研究中心 > 中国科学院生态环境研究中心 > 环境化学与生态毒理学国家重点实验室

	Low concentrations of bisphenol a suppress thyroid hormone receptor transcription through a nongenomic mechanism
	Sheng, Zhi-Guo ; Tang, Yuan ; Liu, Yu-Xiang ; Yuan, Ye ; Zhao, Bao-Quan ; Chao, Xi-Juan ; Zhu, Ben-Zhan
刊名	Pharmacology & Pharmacy; Toxicology
	2012
卷号	259 期号:1 页码:133-142
关键词	Bisphenol A Thyroxine Triiodothyronine TR transcription N-CoR SMRT
ISSN号	0041-008X
中文摘要	Bisphenol (BPA) is one of the highest-volume chemicals produced worldwide, and human exposure to BPA is thought to be ubiquitous. Various rodent and in vitro studies have shown that thyroid hormone (TH) function can be impaired by BPA. However, it is still unknown if low concentrations of BPA can suppress the thyroid hormone receptor (TR) transcription. The present study aims to investigate the possible suppressing effects of low concentrations of BPA on TR transcription and the involved mechanism(s) in CV-1 cells derived from cercopithecus aethiops monkey kidneys. Using gene reporter assays. BPA at concentrations as low as 10(-9) M suppresses TR or steroid receptor coactivator-1(SRC-1)-enhanced TR transcription, but not reducing TR/SRC-1 interaction in mammalian two-hybrid and glutathione S-transferase pull-down studies. It has been further shown that both nuclear receptor co-repressor (N-CoR) and silencing mediator for retinoid and thyroid hormone receptors (SMRT) are recruited to the TR-beta 1 by BPA in the presence of physiologic concentrations of T3 or T4. However, the overexpression of beta 3 integrin or c-Src significantly reduces BPA-induced recruitment of N-CoR/SMRT to TR or suppression of TR transcription. Furthermore, BPA inhibits the T3/T4-mediated interassociation of the beta 3 integrin/c-Src/MAPK/TR-beta 1 pathways by the co-immunoprecipitation. These results indicate that low concentrations of BPA suppress the TR transcription by disrupting physiologic concentrations of T3/T4-mediated beta 3 integrin/c-Src/MAPK/TR-beta 1 pathways, followed by recruiting N-CoR/SMRT to TR-beta 1, providing a novel insight regarding the TH disruption effects of low concentration BPA. (C) 2011 Elsevier Inc. All rights reserved.
WOS记录号	WOS:000301094800014
公开日期	2014-11-27
内容类型	期刊论文
源URL	[http://ir.rcees.ac.cn/handle/311016/8066]
专题	生态环境研究中心_环境化学与生态毒理学国家重点实验室
推荐引用方式 GB/T 7714	Sheng, Zhi-Guo,Tang, Yuan,Liu, Yu-Xiang,et al. Low concentrations of bisphenol a suppress thyroid hormone receptor transcription through a nongenomic mechanism[J]. Pharmacology & Pharmacy; Toxicology,2012,259(1):133-142.
APA	Sheng, Zhi-Guo.,Tang, Yuan.,Liu, Yu-Xiang.,Yuan, Ye.,Zhao, Bao-Quan.,...&Zhu, Ben-Zhan.(2012).Low concentrations of bisphenol a suppress thyroid hormone receptor transcription through a nongenomic mechanism.Pharmacology & Pharmacy; Toxicology,259(1),133-142.
MLA	Sheng, Zhi-Guo,et al."Low concentrations of bisphenol a suppress thyroid hormone receptor transcription through a nongenomic mechanism".Pharmacology & Pharmacy; Toxicology 259.1(2012):133-142.