In vitro bioassays of non-steroidal phytoestrogens.
Some of the isoflavonoids present in human diet as well as in urine are expected to exert biologic effects as they have been reported to bind to estrogen receptors and to be estrogenic in other species. This report describes the in vitro assessment of estrogenic effects of isoflavonoids using human endometrial cells and tissue. The relative estrogenic potencies (EC50 values) of estradiol, 3 dietary isoflavonoids (coumestrol, genistein and daidzein) and one of their metabolites (equol), were estimated by using a recently developed multiwell plate in vitro bioassay based on the estrogen-specific enhancement of alkaline phosphatase (AlkP) activity in human endometrial adenocarcinoma cells of the Ishikawa-Var I line. The maximal AlkP activity elicited by the isoflavonoids tested was as high as that achieved with estradiol and their effects were suppressed by the antiestrogens 4-hydroxytamoxifen and ICI 164,384. These results indicate that estradiol and the isoflavonoids exert their effects on AlkP by similar interactions with the estrogen receptor, with potencies depending on binding affinities. The estrogenic effect of equol was confirmed by another in vitro bioassay, based on the estrogen-stimulated enhancement of prostaglandin F2 alpha output by fragments of human secretory endometrium.
Department of Obstetrics, Gynecology & Reproductive Science, Mount Sinai School of Medicine, New York, NY 10029-6574.
L
L
Markiewicz
J
J
Garey
H
H
Adlercreutz
E
E
Gurpide
D000230:Adenocarcinoma; D000469:Alkaline Phosphatase / Q000378:metabolism; D001681:Biological Assay; D002839:Chromans / Q000494:pharmacology; D003375:Coumestrol / Q000494:pharmacology*; D015237:Dinoprost / Q000378:metabolism; D016889:Endometrial Neoplasms; D004717:Endometrium / Q000187:drug effects / Q000378:metabolism; D060754:Equol; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D005260:Female; D019833:Genistein; D006801:Humans; D007529:Isoflavones / Q000494:pharmacology*; D053284:Polyunsaturated Alkamides; D013629:Tamoxifen / Q000031:analogs & derivatives / Q000494:pharmacology; D014407:Tumor Cells, Cultured
C007610:4',7-dihydroxy-3,4-dihydroisoflavone; D002839:Chromans; D007529:Isoflavones; D053284:Polyunsaturated Alkamides; D013629:Tamoxifen; C016601:afimoxifene; D004958:Estradiol; D060754:Equol; C004742:daidzein; C051781:ICI 164384; D015237:Dinoprost; D019833:Genistein; D000469:Alkaline Phosphatase; D003375:Coumestrol