In C57Bl/6N Female Mice 17β‐Estradiol Leads to Cardiac Mass and Function Loss via a β‐Catenin Mechanism

Abstract

We recently found that 17β‐estradiol (E2) induced physiological hypertrophic growth in the heart of C57Bl/6J but not of C57Bl/6N female mice. We aimed at characterizing the E2 effects in C57Bl/6N mice hypothesizing that β‐catenin mediates these. Two‐month‐old female C57Bl/6N wild‐type (WT) and cardiac‐specific β‐catenin‐deleted (β‐catΔex2‐6) mice were ovariectomized and randomized to an E2‐containing or soy‐free (CON) diet (n = 7‐13/group). The 3‐month physiological dose of E2 led to a higher relative uterus weight compared with CON (P < 0.001) in both WT and β‐catΔex2‐6 mice. The relative heart weight and cardiomyocyte cross‐sectional area were significantly decreased by E2 compared with CON in WT mice (P < 0.001), while there was no significant effect in β‐catΔex2‐6 mice. Echocardiographic measurements revealed a significant decrease in septum width (P < 0.001), posterior wall thickness (P < 0.01) and fractional shortening (P < 0.05) in E2 treated WT mice compared with CON, while there was no significant change in β‐catΔex2‐6 mice. Immunoblotting analysis of the muscle‐specific RING finger protein 1 (MuRF1) revealed a significant increase in its levels by E2 compared with CON in WT mice (P < 0.05), while there was no significant effect in β‐catΔex2‐6 mice. In conclusion, our surprising findings indicate that in C57Bl/6N mice E2 leads to cardiac mass and function loss via a β‐catenin mechanism.