Interaction of phytoestrogens with estrogen receptors alpha and beta

The human estrogen receptor (hER) exists as two subtypes, hER alpha and hER beta, that differ in the C-terminal ligand-binding domain and in the N-ter minal transactivation domain. In this study, we investigated the estrogenic activities of soy isoflavones after digestion with enteric bacteria in com petition binding assays with hER alpha or hER beta protein, and in a gene e xpression assay using a yeast system. The estrogenic activities of these is oflavones were also investigated by the growth of MCF-7 breast cancer cells . Isoflavone glycoside binds weakly to both receptors and estrogen receptor-d ependent transcriptional expression is poor. The aglycones bind more strong ly to hER beta than to hER alpha The binding affinities of genistein, dihyd rogenistein and equol are comparable to the binding affinity of 17 beta -es tradiol, Equol induces transcription most strongly with hER alpha and hER b eta. The concentration required for maximal gene expression is much higher than expected from the binding affinities of the compounds, and the maximal activity induced by these compounds is about half the activity of 17 beta -estradiol, Although genistin binds more weakly to the receptors and induce s transcription less than does genistein, it stimulates the growth of MCF-7 cells more strongly than does genistein.