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Interactions of Dietary Estrogens with Human Estrogen Receptors and the Effect on Estrogen Receptor-Estrogen Response Element Complex Formation
Georgi N. Nikov, Nancy E. Hopkins, Stephen Boue and William L. Alworth
Environmental Health Perspectives
Vol. 108, No. 9 (Sep., 2000), pp. 867-872
Published by: The National Institute of Environmental Health Sciences
Stable URL: http://www.jstor.org/stable/3434995
Page Count: 6
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Epidemilogic and experimental studies support the hypothesis that dietary estrogens from plant sources (phytoestrogens) may play a role in the prevention of breast and prostate cancer. The molecular mechanisms for such chemopreventive effect are still unclear. We investigated the possibility that phytoestrogens may bind differentially to estrogen receptor proteins (ERα and ERβ) and affect the interactions of the ligand-ER complexes with different estrogen response element (ERE) sequences. We used fluorescence polarization to measure the binding affinities of genistein, coumestrol, daidzein, glyceollin, and zearalenone for human ERα and ERβ. Competition binding experiments revealed higher affinity of the phytoestrogens for ERβ than for ERα. Genistein [median inhibitory concentration 12nM] is the most potent and has the same relative binding affinity for ERβ as 17β-estradiol. We also studied the effect of these phytoestrogens on the ability of ERα and ERβ to associate with specific DNA sequences (EREs). The direct binding of human recombinant estrogen receptors to fluorescein-labeled EREs indicates that phytoestrogens can cause conformational changes in both human ERs, which results in altered affinities of the complexes for the ERE from the Xenopus vitellogenin A2 gene and an ERE from the human pS2 gene.
Environmental Health Perspectives © 2000 The National Institute of Environmental Health Sciences