Interaction of phytoestrogens with estrogen receptors alpha and beta (II).
We investigated the estrogenic activities of isoflavone derivatives in competition binding assays with human estrogen receptor (hER) alpha or hER beta protein, and in a gene expression assay using a yeast system. Coumestrol binds as strongly as 17beta-estradiol to both hERs. Biochanin A, 5-OMe-genistein, formononetin, and tectorigenin bind well to hER beta, but significant binding to hER alpha is only observed with 5-OMe-genistein, formononetin and tectorigenin. The binding of 7-OMe-genistein and irisolidone is poor to both receptors. Among the glucosides, sissotorin binds both receptors and the binding is stronger than genistin. Coumestrol induces transcription as strongly as genistein. Tectorigenin also induces transcription with both hERs. Though biochanin A, 5-OMe-genistein, 7-OMe-genistein, irisolidone and formononetin slightly induce transcription with hER beta, they act as antagonists in the induction of transcription by 17beta-estradiol. The results show that methylation or glucosidation of isoflavones generally inhibits their phytoestrogenic activities.
Morito
Keiko
K
Department of Molecular and Cellular Biology, Faculty of Pharmaceutical Sciences, Kanazawa University, Ishikawa, Japan.
Aomori
Tohru
T
Hirose
Toshiharu
T
Kinjo
Junei
J
Hasegawa
Junichi
J
Ogawa
Sumito
S
Inoue
Satoshi
S
Muramatsu
Masami
M
Masamune
Yukito
Y
D004965:Estrogen Antagonists / Q000494:pharmacology; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004968:Estrogens, Non-Steroidal / Q000494:pharmacology*; D006801:Humans; D007529:Isoflavones / Q000494:pharmacology*; D048789:Phytoestrogens; D028321:Plant Preparations; D011960:Receptors, Estrogen / Q000096:biosynthesis / Q000187:drug effects* / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects; D001616:beta-Galactosidase / Q000096:biosynthesis
D004965:Estrogen Antagonists; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004968:Estrogens, Non-Steroidal; D007529:Isoflavones; D048789:Phytoestrogens; D028321:Plant Preparations; D011960:Receptors, Estrogen; D001616:beta-Galactosidase