| First Author | Belcher SM | Year | 2012 |
| Journal | Endocrinology | Volume | 153 |
| Issue | 2 | Pages | 712-20 |
| PubMed ID | 22166976 | Mgi Jnum | J:181733 |
| Mgi Id | MGI:5313785 | Doi | 10.1210/en.2011-1772 |
| Citation | Belcher SM, et al. (2012) Rapid estrogen receptor-mediated mechanisms determine the sexually dimorphic sensitivity of ventricular myocytes to 17beta-estradiol and the environmental endocrine disruptor bisphenol A. Endocrinology 153(2):712-20 |
| abstractText | Previously we showed that 17beta-estradiol (E(2)) and/or the xenoestrogen bisphenol A (BPA) alter ventricular myocyte Ca(2+) handing, resulting in increased cardiac arrhythmias in a female-specific manner. In the present study, the roles of estrogen receptors (ER) in mediating the rapid contractile and arrhythmogenic effects of estrogens were examined. Contractility was used as an index to assess the impact of E(2) or BPA on Ca(2+) handling in rodent ventricular myocytes. The concentration-response curve for the stimulatory effects of BPA and E(2) on female myocyte was inverted-U shaped. Detectable effects for each compound were observed at 10(-12) M, and the most efficacious concentrations for each were at 10(-9) M. Sensitivity to E(2) and BPA was not observed in male myocytes and was abolished in myocytes from ovariectomized females. Analysis using protein-conjugated E(2) suggests that these rapid actions are induced by membrane-associated receptors. Analysis using selective ER agonists and antagonists and a genetic ERbeta knockout mouse model showed that ERalpha and ERbeta have opposing actions in myocytes and that the balance between ERbeta and ERalpha signaling is the prime regulator of the sex-specific sensitivity toward estrogens. The response of female myocytes to E(2) and BPA is dominated by the stimulatory ERbeta-mediated signaling, and the absence of BPA and E(2) responsiveness in males is due to a counterbalancing-suppressive action of ERalpha. We conclude that the sex-specific sensitivity of myocytes to estrogens and the rapid arrhythmogenic effects of BPA and estradiol in the female heart are regulated by the balance between ERalpha and ERbeta signaling. |
