Janosek J, Hilscherová K, Bláha L, Holoubek I
RECETOX, Masaryk University Brno, Kamenice 3, 625 00 Brno, Czech Republic.
Toxicol In Vitro. 2006 Feb;20(1):18-37. doi: 10.1016/j.tiv.2005.06.001. Epub 2005 Aug 2.
A group of intracellular nuclear receptors is a protein superfamily including arylhydrocarbon AhR, estrogen ER, androgen AR, thyroid TR and retinoid receptors RAR/RXR as well as molecules with unknown function known as orphan receptors. These proteins play an important role in a wide range of physiological as well as toxicological processes acting as transcription factors (ligand-dependent signalling macromolecules modulating expression of various genes in a positive or negative manner). A large number of environmental pollutants and other xenobiotics negatively affect signaling pathways, in which nuclear receptors are involved, and these modulations were related to important in vivo toxic effects such as immunosuppression, carcinogenesis, reproduction or developmental toxicity, and embryotoxicity. Presented review summarizes current knowledge on major nuclear receptors (AhR, ER, AR, RAR/RXR, TR) and their relationship to known in vivo toxic effects. Special attention is focused on priority organic environmental contaminants and experimental approaches for determination and studies of specific toxicity mechanisms.
一组细胞内核受体是一个蛋白质超家族，包括芳烃受体AhR、雌激素受体ER、雄激素受体AR、甲状腺激素受体TR和视黄酸受体RAR/RXR，以及功能未知的分子，即孤儿受体。这些蛋白质作为转录因子（以正向或负向方式调节各种基因表达的配体依赖性信号大分子），在广泛的生理和毒理学过程中发挥重要作用。大量环境污染物和其他外源性物质会对核受体参与的信号通路产生负面影响，这些调节与重要的体内毒性效应有关，如免疫抑制、致癌作用、生殖或发育毒性以及胚胎毒性。本综述总结了关于主要核受体（AhR、ER、AR、RAR/RXR、TR）的现有知识及其与已知体内毒性效应的关系。特别关注的是优先有机环境污染物以及用于确定和研究特定毒性机制的实验方法。
