INSERM, U554, Centre de Biochimie Structurale, Montpellier, France.
Cell Mol Life Sci. 2010 Apr;67(8):1219-37. doi: 10.1007/s00018-009-0249-2. Epub 2010 Jan 9.
Endocrine-disrupting chemicals (EDCs) represent a broad class of exogenous substances that cause adverse effects in the endocrine system by interfering with hormone biosynthesis, metabolism, or action. The molecular mechanisms of EDCs involve different pathways including interactions with nuclear hormone receptors (NHRs) which are primary targets of a large variety of environmental contaminants. Here, based on the crystal structures currently available in the Protein Data Bank, we review recent studies showing the many ways in which EDCs interact with NHRs and impact their signaling pathways. Like the estrogenic chemical diethylstilbestrol, some EDCs mimic the natural hormones through conserved protein-ligand contacts, while others, such as organotins, employ radically different binding mechanisms. Such structure-based knowledge, in addition to providing a better understanding of EDC activities, can be used to predict the endocrine-disrupting potential of environmental pollutants and may have applications in drug discovery.
内分泌干扰化学物质（EDCs）是一大类外源性物质，它们通过干扰激素的生物合成、代谢或作用，对内分泌系统产生不良影响。EDCs 的分子机制涉及不同的途径，包括与核激素受体（NHRs）的相互作用，NHRs 是各种环境污染物的主要靶标。在这里，我们基于目前在蛋白质数据库中可用的晶体结构，综述了最近的研究，这些研究展示了 EDCs 与 NHRs 相互作用并影响其信号通路的多种方式。像雌激素化学物质己烯雌酚一样，一些 EDCs 通过保守的蛋白-配体接触模拟天然激素，而另一些 EDCs，如有机锡，采用截然不同的结合机制。这种基于结构的知识，除了可以更好地理解 EDC 的作用外，还可以用于预测环境污染物的内分泌干扰潜力，并可能在药物发现中得到应用。
