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核受体是内分泌干扰物的主要靶标。

Nuclear receptors are the major targets of endocrine disrupting chemicals.

机构信息

Institut de Recherche en Cancérologie de Montpellier (IRCM), INSERM U1194, ICM, Univ Montpellier, 34090, Montpellier, France.

出版信息

Mol Cell Endocrinol. 2020 Feb 15;502:110665. doi: 10.1016/j.mce.2019.110665. Epub 2019 Nov 21.

Abstract

Endocrine disrupting chemicals (EDCs) are exogenous substances that are suspected to cause adverse effects in the endocrine system mainly by acting through their interaction with nuclear receptors such as the estrogen receptors α and β (ERα and ERβ), the androgen receptor (AR), the pregnan X receptor (PXR), the peroxisome proliferator activated receptors α and γ (PPARα, PPARγ) and the thyroid receptors α and β (TRα and TRβ). More recently, the retinoid X receptors (RXRα, RXRβ and RXRγ), the constitutive androstane receptor (CAR) and the estrogen related receptor γ (ERRγ) have also been identified as targets of EDCs. Finally, nuclear receptors still poorly studied for their interaction with environmental ligands such as the progesterone receptor (PR), the mineralocorticoid receptor (MR), the glucocorticoid receptor (GR), the retinoic acid receptors (RAR α, RARβ and RARγ), the farnesoid X receptor (FXR) and the liver X receptors α and β (LXRα and LXβ) as well are suspected targets of EDCs. Humans are generally exposed to low doses of pollutants, therefore the aim of current research is to identify the targets of EDCs at environmental concentrations. In this review, we analyze recent works referring that nuclear receptors are targets of EDCs and we highlight which EDCs are able to act at low concentrations.

摘要

内分泌干扰化学物质 (EDCs) 是一种外源性物质,它们被怀疑通过与核受体(如雌激素受体 α 和 β (ERα 和 ERβ)、雄激素受体 (AR)、孕烷 X 受体 (PXR)、过氧化物酶体增殖物激活受体 α 和 γ (PPARα、PPARγ) 和甲状腺受体 α 和 β (TRα 和 TRβ))相互作用,主要对内分泌系统产生不良影响。最近,视黄酸 X 受体 (RXRα、RXRβ 和 RXRγ)、组成型雄烷受体 (CAR) 和雌激素相关受体 γ (ERRγ) 也被确定为 EDCs 的靶标。最后,核受体与环境配体(如孕激素受体 (PR)、盐皮质激素受体 (MR)、糖皮质激素受体 (GR)、视黄酸受体 (RARα、RARβ 和 RARγ)、法尼醇 X 受体 (FXR) 和肝 X 受体 α 和 β (LXRα 和 LXβ))的相互作用仍研究甚少,这些受体也被怀疑是 EDCs 的靶标。人类通常暴露于低剂量的污染物,因此当前研究的目的是在环境浓度下识别 EDCs 的靶标。在这篇综述中,我们分析了最近的研究工作,这些研究表明核受体是 EDCs 的靶标,并强调了哪些 EDCs 能够在低浓度下发挥作用。

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