title: Phytoestrogens and mycoestrogens bind to the rat uterine estrogen receptor.
abstract: Consumption of phytoestrogens and mycoestrogens in food products or as dietary supplements is of interest because of both the potential beneficial and adverse effects of these compounds in estrogen-responsive target tissues. Although the hazards of exposure to potent estrogens such as diethylstilbestrol in developing male and female reproductive tracts are well characterized, less is known about the effects of weaker estrogens including phytoestrogens. With some exceptions, ligand binding to the estrogen receptor (ER) predicts uterotrophic activity. Using a well-established and rigorously validated ER-ligand binding assay, we assessed the relative binding affinity (RBA) for 46 chemicals from several chemical structure classes of potential phytoestrogens and mycoestrogens. Although none of the test compounds bound to ER with the affinity of the standard, 17beta-estradiol (E(2)), ER binding was found among all classes of chemical structures (flavones, isoflavones, flavanones, coumarins, chalcones and mycoestrogens). Estrogen receptor relative binding affinities were distributed across a wide range (from approximately 43 to 0.00008; E(2) = 100). These data can be utilized before animal testing to rank order estimates of the potential for in vivo estrogenic activity of a wide range of untested plant chemicals (as well as other chemicals) based on ER binding.
authors.affiliation: Division of Genetic and Reproductive Toxicology, Jefferson Laboratories, National Center for Toxicological Research, Jefferson, AR 72079, USA. wbranham@nctr.fda.gov
authors.forename: William S
authors.initials: WS
authors.lastname: Branham
authors.forename: Stacey L
authors.initials: SL
authors.lastname: Dial
authors.forename: Carrie L
authors.initials: CL
authors.lastname: Moland
authors.forename: Bruce S
authors.initials: BS
authors.lastname: Hass
authors.forename: Robert M
authors.initials: RM
authors.lastname: Blair
authors.forename: Hong
authors.initials: H
authors.lastname: Fang
authors.forename: Leming
authors.initials: L
authors.lastname: Shi
authors.forename: Weida
authors.initials: W
authors.lastname: Tong
authors.forename: Roger G
authors.initials: RG
authors.lastname: Perkins
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Sheehan
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D002478:Cells, Cultured; D004968:Estrogens, Non-Steroidal / Q000378:metabolism*; D005260:Female; D005419:Flavonoids / Q000378:metabolism; D007529:Isoflavones; D048789:Phytoestrogens; D028321:Plant Preparations; D051381:Rats; D017207:Rats, Sprague-Dawley; D011960:Receptors, Estrogen / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014599:Uterus
chemical_list: D004968:Estrogens, Non-Steroidal; D005419:Flavonoids; D007529:Isoflavones; D048789:Phytoestrogens; D028321:Plant Preparations; D011960:Receptors, Estrogen