Interaction of Phytoestrogens with Estrogen Receptors .ALPHA. and .BETA..

Abstract

The human estrogen receptor (hER) exists as two subtypes, hER a a and hER b b, that differ in the C-terminal ligand-binding domain and in the N-terminal transactivation domain. In this study, we investigated the estrogenic activities of soy isoflavones after digestion with enteric bacteria in competition binding assays with hER a a or hER b b protein, and in a gene expression assay using a yeast system. The estrogenic activities of these isoflavones were also investigated by the growth of MCF-7 breast cancer cells.Isoflavone glycoside binds weakly to both receptors and estrogen receptor-dependent transcriptional expression is poor. The aglycones bind more strongly to hER b b than to hER a a. The binding affinities of genistein, dihydrogenistein and equol are comparable to the binding affinity of 17 b b-estradiol. Equol induces transcription most strongly with hER a a and hER b b. 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 b b-estradiol. Although genistin binds more weakly to the receptors and induces transcription less than does genistein, it stimulates the growth of MCF-7 cells more strongly than does genistein.

Plasma phyto-oestrogens and prostate cancer in the European Prospective Investigation into Cancer and Nutrition

“…This association may be mediated by oestrogenic and/or a number of anti-carcinogenic properties, although the biological effects of exposure to phyto-oestrogens in humans remain uncertain (Bingham et al, 1998;Magee and Rowland, 2004;McCann et al, 2005;McCormick et al, 2007). Phyto-oestrogens have a structure similar to mammalian oestrogens and can bind to the oestrogen receptor (Morito et al, 2001;Mueller et al, 2004). Experimental evidence suggests that the interaction of isoflavones with the oestrogen receptor beta (ER-b) might be particularly important in the development of prostate cancer (Morito et al, 2001;McCarty, 2006); compared with daidzein, genistein has a much greater affinity for the ER-b, selectively promoting ER-b signalling which in turn may suppress cellular proliferation and promote differentiation in the prostate (McCarty, 2006;Ricke et al, 2007).…”

“…Phyto-oestrogens have a structure similar to mammalian oestrogens and can bind to the oestrogen receptor (Morito et al, 2001;Mueller et al, 2004). Experimental evidence suggests that the interaction of isoflavones with the oestrogen receptor beta (ER-b) might be particularly important in the development of prostate cancer (Morito et al, 2001;McCarty, 2006); compared with daidzein, genistein has a much greater affinity for the ER-b, selectively promoting ER-b signalling which in turn may suppress cellular proliferation and promote differentiation in the prostate (McCarty, 2006;Ricke et al, 2007). It is unclear though whether the levels of dietary phyto-oestrogen exposure in humans are sufficiently high to exert a biological effect (Liggins et al, 2000b;McCarty, 2006).…”

A biochanin-enriched isoflavone from red clover lowers LDL cholesterol in men

“…It is generally accepted that equol excretors are in the minority (Rowland et al, 2000). The interest in equol derives partly from the fact that equol binds to oestrogen receptors with greater affinity than its parent compound formononetin and equally with that of genistein (Morito et al, 2001).…”

Soy Isoflavone Equol Perpetuates Dextran Sulfate Sodium-Induced Acute Colitis in Mice

“…The binding affinity of equol for estrogen receptors has been found to be similar to that of other isoflavones, but equol induced transcription more strongly than did any other isoflavone. 18) The present study did not determine the target cells and mechanism by which equol perpetrated colitis. However, this study has shown for the first time that a soy isoflavone regulated the inflammatory response in the intestines.…”