Department of Cell Biology, Key Laboratory of Cell Biology, Ministry of Public Health of China, China Medical University, Shenyang 110001, China.
Mol Cell Endocrinol. 2013 Jan 5;365(1):36-43. doi: 10.1016/j.mce.2012.09.001. Epub 2012 Sep 10.
Endocrine disrupting chemicals (EDCs) have emerged as a major public health issue because of their potentially disruptive effects on physiological hormonal actions. SXR (steroid xenobiotic receptor), also known as NR1I2, regulates CYP3A expression in response to exogenous chemicals, such as EDCs, after binding to SXRE (SXR response element). In our study, luciferase assay showed that 14 out of 55 EDCs could enhance SXR-mediated rat or human CYP3A gene transcription nearly evenly, and could also activate rat CYP7A1 gene transcription by cross-interaction of SXR and LXRE (LXRα response element). SXR diffused in the nucleus without ligand, whereas intranuclear foci of liganded SXR were produced. Furthermore, endogenous mRNA expression of CYP3A4 gene was enhanced by the 14 positive EDCs. Our results suggested a probable mechanism of EDCs disrupting the steroid or xenobiotic metabolism homeostasis via SXR.
内分泌干扰化学物质（EDCs）因其对生理激素作用的潜在干扰而成为一个主要的公共卫生问题。SXR（甾体异源生物受体），也称为 NR1I2，在与 SXRE（SXR 反应元件）结合后，可调节 CYP3A 的表达，以应对外源性化学物质，如 EDCs。在我们的研究中，荧光素酶检测表明，55 种 EDC 中的 14 种可几乎均匀地增强 SXR 介导的大鼠或人 CYP3A 基因转录，并且还可以通过 SXR 和 LXRE（LXRα 反应元件）的交叉相互作用激活大鼠 CYP7A1 基因转录。没有配体时 SXR 在核内扩散，而有配体的 SXR 核内焦点被产生。此外，14 种阳性 EDC 可增强内源性 CYP3A4 基因的 mRNA 表达。我们的结果表明，EDCs 通过 SXR 破坏类固醇或异生物质代谢平衡的一种可能机制。
