title: Identification of the potent phytoestrogen glycinol in elicited soybean (Glycine max).
abstract: The primary induced isoflavones in soybean, the glyceollins, have been shown to be potent estrogen antagonists in vitro and in vivo. The discovery of the glyceollins' ability to inhibit cancer cell proliferation has led to the analysis of estrogenic activities of other induced isoflavones. In this study, we investigated a novel isoflavone, glycinol, a precursor to glyceollin that is produced in elicited soy. Sensitive and specific in vitro bioassays were used to determine that glycinol exhibits potent estrogenic activity. Estrogen-based reporter assays were performed, and glycinol displayed a marked estrogenic effect on estrogen receptor (ER) signaling between 1 and 10 microM, which correlated with comparable colony formation of MCF-7 cells at 10 microM. Glycinol also induced the expression of estrogen-responsive genes (progesterone receptor and stromal-cell-derived factor-1). Competitive binding assays revealed a high affinity of glycinol for both ER alpha (IC(50) = 13.8 nM) and ER beta (IC(50) = 9.1 nM). In addition, ligand receptor modeling (docking) studies were performed and glycinol was shown to bind similarly to both ER alpha and ER beta. Taken together, these results suggest for the first time that glycinol is estrogenic and may represent an important component of the health effects of soy-based foods.
authors.affiliation: Southern Regional Research Center, United States Department of Agriculture, New Orleans, Louisiana 70179, USA. sboue@srrc.ars.usda.gov
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Boué
authors.forename: Syreeta L
authors.initials: SL
authors.lastname: Tilghman
authors.forename: Steven
authors.initials: S
authors.lastname: Elliott
authors.forename: M Carla
authors.initials: MC
authors.lastname: Zimmerman
authors.forename: K Y
authors.initials: KY
authors.lastname: Williams
authors.forename: Florastina
authors.initials: F
authors.lastname: Payton-Stewart
authors.forename: Allen P
authors.initials: AP
authors.lastname: Miraflor
authors.forename: Melanie H
authors.initials: MH
authors.lastname: Howell
authors.forename: Betty Y
authors.initials: BY
authors.lastname: Shih
authors.forename: Carol H
authors.initials: CH
authors.lastname: Carter-Wientjes
authors.forename: Chris
authors.initials: C
authors.lastname: Segar
authors.forename: Barbara S
authors.initials: BS
authors.lastname: Beckman
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Wiese
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Cleveland
authors.forename: John A
authors.initials: JA
authors.lastname: McLachlan
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Burow
mesh_terms: D001667:Binding, Competitive; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004353:Drug Evaluation, Preclinical; D004967:Estrogens / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology; D005285:Fermentation / Q000502:physiology*; D044948:Flavonols / Q000737:chemistry / Q000302:isolation & purification* / Q000378:metabolism / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008954:Models, Biological; D008958:Models, Molecular; D048789:Phytoestrogens / Q000737:chemistry / Q000302:isolation & purification* / Q000378:metabolism / Q000494:pharmacology; D036343:Pterocarpans / Q000737:chemistry; D011960:Receptors, Estrogen / Q000378:metabolism / Q000502:physiology; D013025:Glycine max / Q000737:chemistry* / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D004967:Estrogens; D044948:Flavonols; D048789:Phytoestrogens; D036343:Pterocarpans; D011960:Receptors, Estrogen; C017343:glyceollin; C540862:glycinol