Estrogen Differentially Affects Expression of Calcium Handling Genes in Female and Male Adult Cardiomyocytes

Abstract

Premenopausal women have a lower risk of developing heart disease compared with postmenopausal women and age-matched men. However, the debate about whether estrogen is cardioprotective is ongoing due to conflicting results from basic science and clinical trials as well as signaling pathways that make interpretation of effects difficult. Calcium handling in the contracting cells of the heart, the cardiomyocytes, is one of the most important pathways involved in heart function. We sought to determine if calcium-handling genes are regulated by estrogen in a sexually dimorphic manner to explain differences in heart health between men and women.  Cardiomyocytes were isolated from the hearts of healthy male and female rats and were treated with different doses of estrogen (300pM, 10nM). Expression of a set of calcium handling genes was then measured to determine the effect of estrogen. Our results demonstrate that estrogen differentially regulates calcium-handling genes in female and male cells, an effect that is also dose-dependent. To our knowledge, this is the first study to examine expression of this comprehensive set of calcium-handling genes in response to estrogen and to consider its effects separately on cardiomyocytes isolated from males and females.