Interactions of phytoestrogens with estrogen receptors alpha and beta (III). Estrogenic activities of soy isoflavone aglycones and their metabolites isolated from human urine.
Two glucuronides (4'-O-, and 7-O-) and a glucuronyl (7-O-) sulfate (4'-O-) of genistein, two glucuronides (4'-O-, and 7-O-) and a glucuronyl (7-O-) sulfate (4'-O-) of daidzein, 7-O-glucuronides of glycitein, dihydrodaidzein and O-desmethylangolensin were isolated from the urine of volunteer subjects fed soy bean curds (Tofu). The estrogenic activities, i.e., i) the effect on the estrogen-dependent growth of MCF-7 cells, ii) the binding ability to human estrogen receptors (hERs) alpha and beta, and iii) the effect on hER-dependent beta-galactosidase induction, of these isoflavone metabolites were examined. Two synthetic isoflavone aglycones (dihydrodaidzein and O-desmethylangolensin) and four synthetic sulfates (4'-O- and 4'-, 7-di-O-) of genistein and daidzein were also studied for their estrogenic activities for the purpose of comparison. With respect to estrogenic acivity, the tested isoflavone metabolites were classified into three groups. The first group shows a very poor stimulatory effect toward the growth of MCF-7 cells, binding activity, and beta-galactosidase induction. The sulfates belong to this group. The second group shows a moderate binding activity but poor stimulation and beta-galactosidase induction. Some glucuronyl conjugates belong to this group. The last group shows a moderate stimulation and beta-galactosidase induction but poor binding activity. A mixed type of conjugates having glucuronyl and sulfony moieties belong to this group.
Kinjo
Junei
J
Faculty of Pharmaceutical Sciences, Fukuoka University, 8-19-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan. kinjojun@fukuoka-u.ac.jp
Tsuchihashi
Ryota
R
Morito
Keiko
K
Hirose
Toshiharu
T
Aomori
Tohru
T
Nagao
Tsuneatsu
T
Okabe
Hikaru
H
Nohara
Toshihiro
T
Masamune
Yukito
Y
D001667:Binding, Competitive; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004790:Enzyme Induction; D047628:Estrogen Receptor alpha / Q000187:drug effects* / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007529:Isoflavones / Q000494:pharmacology* / Q000652:urine; D048789:Phytoestrogens / Q000494:pharmacology*; D045730:Soy Foods; D001616:beta-Galactosidase / Q000096:biosynthesis
D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D007529:Isoflavones; D048789:Phytoestrogens; D001616:beta-Galactosidase