Sex‐specific regulation of contractile function by 17β‐estradiol in mouse cardiomyocytes

Abstract

This study aimed at investigating the regulation of the expression of myosin regulatory light chain (Mrlc) interacting protein (Mylip) gene by 17β-estradiol (E2) and the role of this sex hormone in contractile function. Eleven-month old male C57BL/6J mice were injected intraperitonealy with 10−8 M E2 (n = 6) or vehicle (Ctrl; n = 4) and female C57BL/6J mice of 13–14 months with E2 (n = 8) or vehicle (Ctrl; n = 5). Five hours after injection, cardiomyocytes (CMs) were isolated and were either frozen in TRIzol reagent for RNA isolation or used for cell shortening measurements. Quantitative real-time PCR revealed that E2-treated male CMs had higher Mylip levels than Ctrl CMs (adjusted P = 0.05), while E2 had no effect in Mylip levels of female CMs compared to Ctrl CMs. In addition, there was a decreased abundance in Mrlc in male CMs compared to Ctrl CMs (adjusted P < 0.001), while Mrlc levels did not change in the CMs of female mice. Recordings of unloaded cell shortening at 1, 2 and 4 Hz demonstrated that the treatment with E2 impaired contractile function in male CMs compared to Ctrl CMs at 1 Hz (adjusted P < 0.01) and at 2 Hz (adjusted P < 0.05), while there was an increasing trend in cell contraction of female CMs compared to Ctrl CMs, which reached statistical significance only at 1 Hz (adjusted P = 0.05). In conclusion, we have identified a CM- and sex-specific effect of E2 that regulates contractile function.