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Title: INTERACTIONS OF DIETARY ESTROGENS WITH HUMAN ESTROGEN RECEPTORS AND THE EFFECT ON ESTROGEN RECEPTOR-ESTROGEN RESPONSE ELEMENT COMPLEX FORMATION

Author
item NIKOV, GEORGI - TULANE UNIVERSITY, NOLA
item HOPKINS, NANCY - MILLSAPS COLLEGE, JACKSON
item Boue, Stephen
item ALWORTH, WILLIAM - TULANE UNIVERSITY, NOLA

Submitted to: Environmental Health Perspectives
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/3/2000
Publication Date: 9/1/2000
Citation: Nikov, G.N., Hopkins, N.E., Boue, S.M., Alworth, W.L. 2000. Interactions of dietary estrogens with human estrogen receptors and the effect on estrogen receptor-estrogen response element complex formation. Environmental Health Perspectives. 108(9):867-872.

Interpretive Summary: Studies have shown that dietary estrogens from plant sources (phytoestrogens) may play a role in the prevention of breast and prostate cancer. However, the exact mechanisms for this protective ability are unclear. This study explores the possibility that phytoestrogens may bind differently to two known receptors that recognize the female hormone estrogen. Similar to a lock and key, estrogen binds to two specific receptors in the body. Once bound to these receptors, this complex may interact differently with DNA sequences that affect cancer growth. In this report it was found that phytoestrogens bound preferentially to one of the two receptors. Also, it was found that phytoestrogens bind differently to this estrogen receptor and affect the ability of this complex to bind to specific DNA sequences. This research will benefit human health in general and will lead to a better understanding of the role of phytoestrogens in the prevention of certain cancers.

Technical Abstract: Experimental studies support the hypothesis that dietary estrogens (phytoestrogens) may play a role in the prevention of breast and prostate cancer, however the exact molecular mechanisms for this protective ability are still unclear. We have investigated the possibility that phytoestrogens may bind differentially to estrogen receptor proteins (ERalpha and ERbeta) and affect the interactions of the ligand-ER complexe with different ERE sequences. Fluorescence polarization was used to measure the binding affinities of genistein, coumestrol, daidzein, glyceollin, and zearalenone for human ERalpha and ERbeta. Competition binding experiments revealed higher binding affinity of the phytoestrogens for ERbeta than ERalpha with genistein as the most potent (IC50 12nM). We have also studied the effect of these phytoestrogens on the ability of ERalpha and ERbeta to associate with specific DNA sequences (EREs). Direct tbinding of human recombinant estrogen receptors to fluorescein-labeled estrogen response elements (EREs) indicate that phytoestrogens can cause conformational changes in both human estrogen receptors which result in altered affinities of the complexes for the ERE from the Xenopus vit A2 gene and an ERE from human pS2 gene.