title: Glyceollins and dehydroglyceollins isolated from soybean act as SERMs and ER subtype-selective phytoestrogens.
abstract: Seven prenylated 6a-hydroxy-pterocapans and five prenylated 6a,11a-pterocarpenes with different kinds of prenylation were purified from an ethanolic extract of fungus-treated soybean sprouts. The activity of these compounds toward both human estrogen receptors (hERα and hERβ) was determined in a yeast bioassay and the activity toward hERα was additionally tested in an U2-OS based hERα CALUX bioassay. In the yeast bioassay, compounds with chain prenylation showed in general an agonistic mode of action toward hERα, whereas furan and pyran prenylation led to an antagonistic mode of action. Five of these antagonistic compounds had an agonistic mode of action in the U2-OS based hERα CALUX bioassay, implying that these compounds can act as SERMs. The yeast bioassay also identified 8 ER subtype-selective compounds, with either an antagonistic mode of action or no response toward hERα and an agonistic mode of action toward hERβ. The ER subtype-selective compounds were characterized by 6a-hydroxy-pterocarpan or 6a,11a-pterocarpene backbone structure. It is suggested that either the extra D-ring or the increase in length to 12-13.5Å of these compounds is responsible for an agonistic mode of action toward hERβ and, thereby, inducing ER subtype-selective behavior.
authors.affiliation: Laboratory of Food Chemistry, Wageningen University, Wageningen, The Netherlands.
authors.forename: Milou G M
authors.initials: MG
authors.lastname: van de Schans
authors.affiliation: Laboratory of Food Chemistry, Wageningen University, Wageningen, The Netherlands. Electronic address: jean-paul.vincken@wur.nl.
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Vincken
authors.affiliation: Wageningen NMR Centre, Wageningen University, Wageningen, The Netherlands.
authors.forename: Pieter
authors.initials: P
authors.lastname: de Waard
authors.affiliation: Business Unit of Toxicology and Bioassays, RIKILT-Institute of Food Safety, Wageningen, The Netherlands.
authors.forename: Astrid R M
authors.initials: AR
authors.lastname: Hamers
authors.affiliation: Business Unit of Toxicology and Bioassays, RIKILT-Institute of Food Safety, Wageningen, The Netherlands.
authors.forename: Toine F H
authors.initials: TF
authors.lastname: Bovee
authors.affiliation: Laboratory of Food Chemistry, Wageningen University, Wageningen, The Netherlands.
authors.forename: Harry
authors.initials: H
authors.lastname: Gruppen
mesh_terms: D002460:Cell Line; D047628:Estrogen Receptor alpha / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D048789:Phytoestrogens / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D054876:Prenylation; D036343:Pterocarpans / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D020845:Selective Estrogen Receptor Modulators / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D013025:Glycine max / Q000737:chemistry*
chemical_list: D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D048789:Phytoestrogens; D036343:Pterocarpans; D020845:Selective Estrogen Receptor Modulators; C017343:glyceollin
keywords: 6a,11a-Pterocarpene; 6a-Hydroxy-pterocarpan; Molar extinction coefficient; Prenylation; hER yeast bioassay; hERα-CALUX