Dioxin induces an estrogen-like, estrogen receptor-dependent gene expression response in the murine uterus
Dioxin induces an estrogen-like, estrogen receptor-dependent gene expression response in the murine uterus
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DOI：
10.1124/mol.105.019638
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发表时间：
2006-05-01
影响因子：
3.6
通讯作者：
Zacharewski, TR
中科院分区：
文献类型：
--
作者：
Boverhof, DR;Kwekel, JC;Zacharewski, TR
2，3，7，8-四氯二苯并-对-二恶英（TCDD）是一种普遍存在的环境污染物，其以组织、性别、年龄和物种特异性方式引起广泛的毒性，包括雌激素信号的改变。这些效应中的许多（如果不是全部的话）涉及通过芳烃受体（AhR）（配体激活的转录因子）的激活介导的基因表达的变化。最近的数据表明，TCDD也可能通过与雌激素受体（ER）的相互作用引起AhR介导的雌激素活性。为了进一步研究TCDD的雌激素活性，我们使用切除卵巢的C57 BL/6小鼠进行了子宫基因表达的全面时程分析。TCDD与乙炔雌二醇（EE）的时间子宫转录反应的比较显示，TCDD介导的基因表达变化的很大比例也响应EE。此外，预处理的小鼠与纯ER拮抗剂ICI 182 780（芙仕得）抑制基因表达反应EE和TCDD，提供了额外的证据，这些转录反应涉及ER。
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a ubiquitous environmental contaminant that elicits a broad range of toxicities in a tissue-, sex-, age-, and species-specific manner, including alterations in estrogen signaling. Many, if not all, of these effects involve changes in gene expression mediated via the activation of the aryl hydrocarbon receptor (AhR), a ligand activated transcription factor. Recent data indicate that TCDD may also elicit AhR-mediated estrogenic activity through interactions with the estrogen receptor (ER). In an effort to further characterize the estrogenic activity of TCDD, a comprehensive time-course analysis of uterine gene expression was conducted using ovariectomized C57BL/6 mice. Comparison of the temporal uterine transcriptional response to TCDD with that of ethynyl estradiol (EE) revealed a large proportion of the TCDD-mediated gene expression changes were also responsive to EE. Furthermore, pretreatment of mice with the pure ER antagonist ICI 182 780 (faslodex) inhibited gene expression responses to both EE and TCDD, providing additional evidence that these transcriptional responses involve the ER.