Estrogen receptor profiling and activity in cardiac myocytes

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 ER alpha RNA (but no ER beta RNA) in cardiac myocytes using two independent methods. The vast majority of full-length ER alpha protein (ER alpha 66) localizes to cardiac myocyte nuclei where it is competent to activate transcription. Alternate isoforms of ER alpha encoded by the same genomic locus (ER alpha 46 and ER alpha 36) have differential transcriptional activity in cardiac myocytes but also primarily localize to nuclei. In contrast to other reports, no ER alpha isoform is competent to activate MAPK or PI3K signaling in cardiac myocytes. Together these data support a role for ER alpha at the level of transcription in cardiac myocytes. (C) 2016 Elsevier Ireland Ltd. All rights reserved.