Castration reduces mRNA levels for calcium regulatory proteins in rat heart

Sex-related differences in the cardiac phenotype have been well established. This study was designed to determine whether androgens regulate myocardial gene expression and play a role in the sex-related differences in the myocardial phenotype. Gonadectomized male rats were treated with testosterone, and myocardial gene expression was examined in whole heart using quantitative real-time PCR. Gonadectomy produced a substantial decrease in mRNA levels for the androgen receptor, Na(+)/Ca(2+) exchanger, L- type calcium channel, and beta(1)-adrenergic receptor (beta(1)AR). Supplementation of testosterone in castrates produced a fivefold increase in androgen receptor mRNA levels. Testosterone treatment of castrates produced almost a sixfold increase in Na(+)/Ca(2+) exchanger mRNA, a tenfold increase in Ltype calcium channel mRNA accumulation, and a fourfold increase in beta(1)AR mRNA levels. Increased calcium channel expression, beta(1)AR expression, and Na(+)/Ca(2+) exchanger expression together may alter cytosolic calcium. These results provide the first evidence that testosterone regulates expression of myocardial calcium regulating genes and thus may play a role in modulating the cardiac phenotype in males.