title: Transcriptional regulation by phytoestrogens in neuronal cell lines.
abstract: Widespread epidemiological data support the notion that high isoflavone intake is safe and may provide health benefits similar to estrogen. Evidence from rodents shows that certain phytoestrogens can act as estrogen receptor (ER) ligands in the brain. This study sought to determine the estrogenic profile of food-borne phytoestrogens in neuronal cell lines using physiologically attainable concentrations. At sub-micromolar concentrations genistein, daidzein, and zearalenone stimulated ERalpha and ERbeta-dependent transcription in Neuro2A cells co-transfected with ERs and simple and complex estrogen-response-element (ERE) containing promoters, although compounds were more active in the presence of ERbeta. In SN56, neuronblastoma cells expressing endogenous ERs, only genistein mimicked estrogen regulation of progesterone receptor steady state mRNA levels. Unlike pharmaceutical SERMs, phytoestrogens did not stimulate an AP-1-dependent promoter. Micromolar concentrations of phytoestrogens did not antagonize physiological estrogen concentrations or antagonist activation of an AP-1-dependent promoter. These results demonstrate that food-borne phytoestrogens, particularly those found in soy, act as ERE-, but not AP-1-dependent transcriptional activators in neurons in the absence of estrogen, and dietary levels of these compounds do not act as antagonists to physiological estrogen concentrations.
authors.affiliation: Department of Physiology, Medical College of Georgia, 1120 15th Street, CL2130, Augusta, GA 30912-3000, USA. dschreihofer@mail.mcg.edu
authors.forename: Derek A
authors.initials: DA
authors.lastname: Schreihofer
mesh_terms: D000818:Animals; D002460:Cell Line; D005786:Gene Expression Regulation / Q000187:drug effects*; D019833:Genistein / Q000494:pharmacology; D007529:Isoflavones / Q000494:pharmacology; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D048789:Phytoestrogens / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011960:Receptors, Estrogen; D020218:Response Elements; D020845:Selective Estrogen Receptor Modulators; D018808:Transcription Factor AP-1; D014158:Transcription, Genetic / Q000187:drug effects*; D015025:Zearalenone / Q000494:pharmacology
chemical_list: D007529:Isoflavones; D048789:Phytoestrogens; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D020845:Selective Estrogen Receptor Modulators; D018808:Transcription Factor AP-1; D015025:Zearalenone; C004742:daidzein; D019833:Genistein