受体功能区结构与环境内分泌干扰效应生物差异的关系

环境中存在的多种内分泌干扰物能够与生物体内的天然激素受体选择性结合并产生多种生物效应,由于受体功能区三维结构的不同,其内分泌干扰活性存在着种间、种内、组织间等的种种差异,限制了不同物种间毒性效应的外推研究,增加了环境内分泌干扰物筛选和风险评价的难度.论文综述了基于受体介导的环境内分泌干扰物生物活性与相应受体选择性及受体功能区结构关系的研究进展,并利用分子模拟方法分析探讨了雌激素受体与部分化合物结合作用模式,讨论了目前存在的问题,对以后有关方面的研究提出了建议.

Relationship between the Domain Structures of Several Nuclear Receptors and the Effect Differences of Environmental Endocrine Disrupting Chemicals

A great number of endocrine disrupting chemicals(EDCs)can mimic or affect the interactions between natural hormones and their receptors and cause many biochemical and toxicity effects. Due to the minor changes in the domain structure of related receptors, the endocrine disrupting effects of some chemicals seem to be diverse, showing species-, strains-, tissues-specific characteristics. All of these phenomena increase the complexities of the explanation to the molecular mechanisms of the endocrine disrupting and toxicity effects of EDCs. Recent research findings about the relationship between the essential structures of several nuclear receptors and the adverse biological effects of endocrine disrupters were mainly reviewed in this paper. In addition, receptor binding energies for different compounds were calculated, and simulated binding modes were explored by molecular simulation. Further mechanistic studies should be conducted to get insight into the central functional structures of related proteins involved in the various endocrine disruptions and the properties of variable suspicious EDCs. Moreover, 3D-QSAR is a powerful implement to understand it. Besides, the complex mechanisms of low-dose and high-dose effects and the transferring and metabolizing processes of these EDCs should be concerned.