title: Comparative effects of R- and S-equol and implication of transactivation functions (AF-1 and AF-2) in estrogen receptor-induced transcriptional activity.
abstract: Equol, one of the main metabolites of daidzein, is a chiral compound with pleiotropic effects on cellular signaling. This property may induce activation/inhibition of the estrogen receptors (ER) a or b, and therefore, explain the beneficial/deleterious effects of equol on estrogen-dependent diseases. With its asymmetric centre at position C-3, equol can exist in two enantiomeric forms (R- and S-equol). To elucidate the yet unclear mechanisms of ER activation/inhibition by equol, we performed a comprehensive analysis of ERa and ERb transactivation by racemic equol, as well as by enantiomerically pure forms. Racemic equol was prepared by catalytic hydrogenation from daidzein and separated into enantiomers by chiral HPLC. The configuration assignment was performed by optical rotatory power measurements. The ER-induced transactivation by R- and S-equol (0.1-10 µM) and 17b-estradiol (E2, 10 nM) was studied using transient transfections of ERα and ERβ in CHO, HepG2 and HeLa cell lines. R- and S-equol induce ER transactivation in an opposite fashion according to the cellular context. R-equol and S-equol are more potent in inducing ERα in an AF-2 and AF-1 permissive cell line, respectively. Involvement of ERα transactivation functions (AF-1 and AF-2) in these effects has been examined. Both AF-1 and AF-2 are involved in racemic equol, R-equol and S-equol induced ERα transcriptional activity. These results could be of interest to find a specific ligand modulating ER transactivation and could contribute to explaining the diversity of equol actions in vivo.
authors.affiliation: ENITA de Bordeaux, Unité Micronutriments Reproduction Santé, Gradignan, France. s-poix-shinkaruk@enitab.fr
authors.forename: Svitlana
authors.initials: S
authors.lastname: Shinkaruk
authors.forename: Charlotte
authors.initials: C
authors.lastname: Carreau
authors.forename: Gilles
authors.initials: G
authors.lastname: Flouriot
authors.forename: Catherine
authors.initials: C
authors.lastname: Bennetau-Pelissero
authors.forename: Mylène
authors.initials: M
authors.lastname: Potier
mesh_terms: D060754:Equol / Q000138:chemical synthesis / Q000494:pharmacology*; D047628:Estrogen Receptor alpha / Q000187:drug effects / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D048789:Phytoestrogens / Q000138:chemical synthesis / Q000494:pharmacology*; D011960:Receptors, Estrogen / Q000187:drug effects* / Q000378:metabolism; D015533:Transcriptional Activation / Q000187:drug effects*
chemical_list: D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D048789:Phytoestrogens; D011960:Receptors, Estrogen; D060754:Equol