Chandsawangbhuwana Charlie, Baker Michael E
Department of Bioengineering, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0693, United States.
Department of Medicine, 0693, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0693, United States.
Steroids. 2014 Feb;80:37-43. doi: 10.1016/j.steroids.2013.11.019. Epub 2013 Dec 5.
Coumestrol, a phytoestrogen found in alfalfa, clover, and beans, has nM affinity for both estrogen receptor-α [ERα] and ERβ. Recently, a novel activity of coumestrol was reported: coumestrol binding to human ERβ represses microglia-mediated inflammation, which is associated with various neurodegenerative diseases, such as multiple sclerosis. In contrast, estradiol binding to ERβ had little or no effect on repression of microglia-mediated inflammation. Coumestrol and estradiol have several structural differences, which suggest that each ligand could induce different conformations in ERβ and, thus, different transcriptional responses in brain microglia. To begin to understand how coumestrol binds to ERβ and ERα, we constructed 3D models of coumestrol with human ERβ and ERα, which were compared to the structures of these ERs with estradiol. Of four possible orientations of coumestrol in ERα and ERβ, one orientation had the most favorable contacts with both ERs. Other phytochemicals may activate ERβ and inhibit inflammation in brain microglia and be useful therapeutics for inflammatory conditions in the brain.
香豆雌酚是一种存在于苜蓿、三叶草和豆类中的植物雌激素，对雌激素受体α[ERα]和ERβ均具有纳摩尔亲和力。最近，有报道称香豆雌酚具有一种新活性：香豆雌酚与人ERβ结合可抑制小胶质细胞介导的炎症，而这种炎症与多种神经退行性疾病（如多发性硬化症）相关。相比之下，雌二醇与ERβ结合对抑制小胶质细胞介导的炎症几乎没有影响。香豆雌酚和雌二醇存在一些结构差异，这表明每种配体可能会在ERβ中诱导不同的构象，从而在脑小胶质细胞中引发不同的转录反应。为了开始了解香豆雌酚如何与ERβ和ERα结合，我们构建了香豆雌酚与人ERβ和ERα的三维模型，并将其与这些ER与雌二醇的结构进行了比较。在香豆雌酚于ERα和ERβ中的四种可能取向中，有一种取向与两种ER的接触最为有利。其他植物化学物质可能会激活ERβ并抑制脑小胶质细胞中的炎症，从而成为治疗脑部炎症性疾病的有效药物。
