Balaguer Patrick, Delfosse Vanessa, Grimaldi Marina, Bourguet William
Institut de recherche en cancérologie de Montpellier (IRCM), 34298 Montpellier, France; Inserm, U1194, 34298 Montpellier, France; Institut régional du cancer de Montpellier (ICM), 34298 Montpellier, France; Université de Montpellier, 34090 Montpellier, France.
Université de Montpellier, 34090 Montpellier, France; Inserm U1054, 34090 Montpellier, France; CNRS UMR5048, Centre de biochimie structurale, 34090 Montpellier, France.
C R Biol. 2017 Sep-Oct;340(9-10):414-420. doi: 10.1016/j.crvi.2017.08.002.
Endocrine-disrupting chemicals (EDCs) represent a broad class of exogenous substances that cause adverse effects in the endocrine system mainly by interacting with nuclear hormone receptors (NRs). Humans are generally exposed to low doses of pollutants, and current researches aim at deciphering the mechanisms accounting for the health impact of EDCs at environmental concentrations. Our correlative analysis of structural, interaction and cell-based data has revealed a variety of, sometimes unexpected, binding modes, reflecting a wide range of EDC affinities and specificities. Here, we present a few representative examples to illustrate various means by which EDCs achieve high-affinity binding to NRs. These examples include the binding of the mycoestrogen α-zearalanol to estrogen receptors, the covalent interaction of organotins with the retinoid X- and peroxisome proliferator-activated receptors, and the cooperative binding of two chemicals to the pregnane X receptor. We also discuss some hypotheses that could further explain low-concentration effects of EDCs with weaker affinity towards NRs.
内分泌干扰化学物质（EDCs）是一类广泛的外源性物质，主要通过与核激素受体（NRs）相互作用对内分泌系统产生不利影响。人类通常暴露于低剂量污染物中，目前的研究旨在破解环境浓度下EDCs对健康产生影响的机制。我们对结构、相互作用和细胞数据的关联分析揭示了多种，有时甚至是意想不到的结合模式，反映出EDCs广泛的亲和力和特异性。在此，我们给出一些代表性例子来说明EDCs与NRs实现高亲和力结合的各种方式。这些例子包括霉菌雌激素α-玉米赤霉醇与雌激素受体的结合、有机锡与视黄酸X受体和过氧化物酶体增殖物激活受体的共价相互作用，以及两种化学物质与孕烷X受体的协同结合。我们还讨论了一些假说，这些假说可以进一步解释对NRs亲和力较弱的EDCs的低浓度效应。
