内分泌干扰物与哺乳动物核受体的相互作用
Interaction of Endocrine Disrupting Chemicals with Mammalian Nuclear Receptors
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摘要: 内分泌干扰物(EDCs)作用于哺乳动物生殖轴或甲状腺轴,影响生长、发育、繁殖、免疫等生理过程并诱发疾病。核受体介导途径是EDCs发挥内分泌干扰作用的最重要方式。在介绍EDCs对哺乳动物的毒性效应与机制的基础上,详细归纳了EDCs与核受体的相互作用,并总结了这一研究领域适用的研究方法。发现采用理论计算模拟、表面等离子共振、荧光偏振、细胞增殖、报告基因等技术方法,目前已经明确了邻苯二甲酸酯类、双酚类、有机氯农药等EDCs能够竞争结合雌激素受体、雄激素受体和/或甲状腺激素受体,以此为作用靶点通过受体介导途径发挥内分泌干扰效应。基于目前的研究现状,我们认为未来的研究应更加注重EDCs与孕激素受体及维甲酸受体的相互作用、膜受体介导途径以及体内实验与体外实验的有机结合。Abstract: Endocrine disrupting chemicals (EDCs) act on the mammalian reproductive axis or thyroid axis to affect physiological processes such as growth, development, reproduction, immunity and induce disease. The nuclear receptor-mediated pathways are the most important ways in which EDCs exert endocrine disrupting actions. In this paper, based on a brief introduction of the toxic effects and mechanisms of EDCs on mammals, the interactions between EDCs and nuclear receptors are summarized in detail, and then the research methods applicable to this field of study are presented. Using theoretical computational simulations, surface plasmon resonance, fluorescence polarization, cell proliferation, reporter genes and other technical approaches, it is now clear that EDCs such as phthalates, bisphenols and organochlorine pesticides can compete for binding to estrogen receptor, androgen receptor and/or thyroid hormone receptor as targets to exert endocrine disrupting effects through receptor-mediated pathways. Based on the current state of research, we believe that future studies should focus more on the interaction between EDCs and other nuclear receptors such as progesterone receptor and retinoic acid receptor, membrane receptor-mediated pathways, and the combination of in vivo and in vitro experiments.
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