Regulation of human estrogen receptor by phytoestrogens in yeast and human cells.
Phytoestrogens are defined as plant substances that are structurally or functionally similar to estrogen. They are present in many foods and their higher consumption in certain populations has been correlated with protection against many diseases including coronary heart disease, breast cancer and endometrial and ovarian cancer. In this report, ten phytoestrogens with diverse chemical structures were studied for their binding to the human estrogen receptor and their transcription activation properties in yeast and mammalian cells. Our results showed that some of these compounds bind with relatively high affinity to the estrogen receptor and activate the receptor in the yeast and mammalian cell system. In addition, none of these compounds showed anti-estrogenic activity. We conclude that the yeast system accurately predicts the estrogenic activity of compounds with diverse chemical structures in mammalian cells. In addition, our data with phytoestrogens that do not show transcription activation properties raise the possibility that these compounds may exert their biological effects through pathways different from the classical estrogen signalling mechanism.
Breithofer
A
A
Institute of Applied Microbiology, University of Agriculture, Forestry and Biotechnology, Vienna, Austria.
Graumann
K
K
Scicchitano
M S
MS
Karathanasis
S K
SK
Butt
T R
TR
Jungbauer
A
A
D001667:Binding, Competitive; D006528:Carcinoma, Hepatocellular; D003001:Cloning, Molecular; D004958:Estradiol / Q000378:metabolism; D004968:Estrogens, Non-Steroidal / Q000494:pharmacology*; D006801:Humans; D007529:Isoflavones; D007700:Kinetics; D008113:Liver Neoplasms; D048789:Phytoestrogens; D028321:Plant Preparations; D011869:Radioligand Assay; D011960:Receptors, Estrogen / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000187:drug effects / Q000378:metabolism; D012441:Saccharomyces cerevisiae; D015533:Transcriptional Activation; D014162:Transfection; D014407:Tumor Cells, Cultured; D001616:beta-Galactosidase / Q000096:biosynthesis / Q000235:genetics
D004968:Estrogens, Non-Steroidal; D007529:Isoflavones; D048789:Phytoestrogens; D028321:Plant Preparations; D011960:Receptors, Estrogen; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D004958:Estradiol; D001616:beta-Galactosidase