In vivo effects of 17β-estradiol on cardiac Na+/K+-ATPase expression and activity in rat heart

•Estradiol influences the activity/expression of Na+/K+-ATPase in vitro.•We propose that estradiol-mediated regulation of Na+/K+-ATPase involves Akt and ERK1/2 activation in vivo.•This work will aid the development of new therapeutic strategies for the treatment of heart disease.

In this study the in vivo effects of estradiol in regulating Na+/K+-ATPase function in rat heart was studied. Adult male Wistar rats were treated with estradiol (40 μg/kg, i.p.) and after 24 h the animals were sacrificed and the heart excised. Following estradiol administration, cardiac Na+/K+-ATPase activity, expression of the α1 subunit, and phosphorylation of the α1 subunit were significantly increased. These animals also had significantly decreased levels of digoxin-like immunoreactive factor(s). Na+ levels were also significantly reduced but to a level that was still within the normal physiological range, highlighting the ability of the Na+/K+-ATPase to balance the ionic composition following treatment with estradiol. Estradiol treated rats also showed increased phosphorylation of protein kinase B (Akt), and extracellular-signal-regulated kinase 1/2 (ERK1/2). We therefore suggest a role for Akt and/or ERK1/2 in estradiol-mediated regulation of cardiac Na+/K+-ATPase expression and activity in rat heart.

Graphical abstractProposed mechanism of in vivo effects of estradiol upon regulation of Na+/K+-ATPase. Estradiol acts through multiple signaling cascades. These are initiated when estradiol passes through the cell membrane and binds to estrogen receptor. The estradiol–ER complex activates IRS-1, which in turn leads to activation of the p110 catalytic subunit of PI3K. PI3K then phosphorylates and activates Akt and ERK1/2. Both Akt and ERK1/2 are regulate the Na+/K+-ATP-ase activation/expression (and phosphorylation). ER, estrogen receptor; IRS1, insulin receptor substrate 1; PI3K, phosphatydilinositol-3 kinase; Akt, protein kinase B; ERK1/2, extracellular signal-regulated kinases 1 and 2; ↑ increase.Figure optionsDownload full-size imageDownload high-quality image (153 K)Download as PowerPoint slide