RESUMO
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.
Assuntos
Receptor alfa de Estrogênio/efeitos dos fármacos , Receptor beta de Estrogênio/efeitos dos fármacos , Isoflavonas/farmacologia , Fitoestrógenos/farmacologia , Alimentos de Soja , Ligação Competitiva , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Indução Enzimática , Receptor alfa de Estrogênio/metabolismo , Receptor beta de Estrogênio/metabolismo , Humanos , Isoflavonas/urina , beta-Galactosidase/biossínteseRESUMO
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.