title: Estrogen receptor profiling and activity in cardiac myocytes.
abstract: Estrogen signaling appears critical in the heart. However a mechanistic understanding of the role of estrogen in the cardiac myocyte is lacking. Moreover, there are multiple cell types in the heart and multiple estrogen receptor (ER) isoforms. Therefore, we studied expression, localization, transcriptional and signaling activity of ERs in isolated cardiac myocytes. We found only ERα RNA (but no ERβ RNA) in cardiac myocytes using two independent methods. The vast majority of full-length ERα protein (ERα66) localizes to cardiac myocyte nuclei where it is competent to activate transcription. Alternate isoforms of ERα encoded by the same genomic locus (ERα46 and ERα36) have differential transcriptional activity in cardiac myocytes but also primarily localize to nuclei. In contrast to other reports, no ERα isoform is competent to activate MAPK or PI3K signaling in cardiac myocytes. Together these data support a role for ERα at the level of transcription in cardiac myocytes.
authors.affiliation: University of Colorado at Boulder, Department of Molecular, Cellular, and Developmental Biology, BioFrontiers Institute, Boulder, CO 80303 USA.
authors.forename: Emily K
authors.initials: EK
authors.lastname: Pugach
authors.affiliation: University of Colorado at Boulder, Department of Molecular, Cellular, and Developmental Biology, BioFrontiers Institute, Boulder, CO 80303 USA.
authors.forename: Christa L
authors.initials: CL
authors.lastname: Blenck
authors.affiliation: University of Colorado, BioFrontiers Advanced Light Microscopy Core, BioFrontiers Institute, Boulder, CO 80309 USA.
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Dragavon
authors.affiliation: University of Colorado at Boulder, Department of Molecular, Cellular, and Developmental Biology, BioFrontiers Institute, Boulder, CO 80303 USA.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Langer
authors.affiliation: University of Colorado at Boulder, Department of Molecular, Cellular, and Developmental Biology, BioFrontiers Institute, Boulder, CO 80303 USA.
authors.forename: Leslie A
authors.initials: LA
authors.lastname: Leinwand
mesh_terms: D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D004958:Estradiol / Q000378:metabolism; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D047629:Estrogen Receptor beta / Q000378:metabolism*; D004967:Estrogens / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D032383:Myocytes, Cardiac / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D020033:Protein Isoforms / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020218:Response Elements / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology
chemical_list: D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004967:Estrogens; D020033:Protein Isoforms; D004958:Estradiol; D019869:Phosphatidylinositol 3-Kinases
keywords: Cardiac myocytes; Estradiol; Estrogen; Estrogen receptors