Testosterone Modulates Cardiomyocyte Ca2+ Handling and Contractile Function

The extent to which sex differences in cardiac function may be attributed to the direct myocardial influence of testosterone is unclear. In this study the effects of gonadal testosterone withdrawal (GDX) and replacement (GDX+T) in rats, on cardiomyocyte shortening and intracellular Ca2+ handling was investigated (0.5 Hz, 25 degrees C). At all extracellular [Ca2+] tested (0.5-2.0 mM), the Ca2+ transient amplitude was significantly reduced (by similar to 50 %) in myocytes of GDX rats two weeks post-gonadectomy. The time course of Ca2+ transient decay was significantly prolonged in GDX myocytes (tau, 455 +/- 80 ms) compared with intact (279 +/- 23 ms) and GDX+T (277 +/- 19 ms). Maximum shortening of GDX myocytes was markedly reduced (by more than 60 %) and relaxation significantly delayed ( by more than 35 %) compared with intact and GDX+T groups. Thus testosterone replacement completely reversed the cardiomyocyte hypocontractility induced by gonadectomy. These results provide direct evidence for a role of testosterone in regulating functional Ca2+ handling and contractility in the heart.