INVITRO BIOASSAYS OF NONSTEROIDAL PHYTOESTROGENS

Some of the isoflavonoids present in human diet as well as in urine ar e expected to exert biologic effects as they have been reported to bin d to estrogen receptors and to be estrogenic in other species. This re port describes the in vitro assessment of estrogenic effects of isofla vonoids using human endometrial cells and tissue. The relative estroge nic potencies (EC50 values) of estradiol, 3 dietary isoflavonoids (cou mestrol, 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 phosp hatase (AlkP) activity in human endometrial adenocarcinoma cells of th e Ishikawa-Var I line. The maximal AlkP activity elicited by the isofl avonoids tested was as high as that achieved with estradiol and their effects were suppressed by the antiestrogens 4-hydroxytamoxifen and IC I 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 estroge nic effect of equol was confirmed by another in vitro bioassay, based on the estrogen-stimulated enhancement of prostaglandin F2alpha output by fragments of human secretory endometrium.