Data from the trial known as
Testosterone in Older Men with
Mobility Limitations (TOM) has indicated an association between
testosterone administration and a greater risk for adverse cardiovascular events. We therefore propose that regular exercise is a cardioprotective alternative that prevents detrimental changes in contractile activation when a deficiency in male
sex hormones exists. Ten-week-old orchidectomized (ORX) rats were subjected to a 9-wk treadmill running program at moderate intensity starting 1 wk after surgery. Although exercise-induced
cardiac hypertrophy was observed both in rats that underwent ORX and
sham surgery, regular exercise enhanced cardiac myofilament Ca(2+) sensitivity and
myosin light-chain 2 phosphorylation only in rats that underwent a
sham operation. Although the rats that had
sham surgery and and given exercise exhibited no change in maximum developed tension, regular running prevented the suppression of maximum active tension in the hearts of ORX rats. Regular exercise also prevented a shift in
myosin heavy chain (MHC)
isoforms toward β-MHC, a reduction in sarco(endo)plasmic reticulum Ca(2+)-
ATPase (SERCA) activity, and an increase in SERCA sensitivity in the hearts of ORX rats. Neither SERCA content nor its modulating component,
phospholamban (PLB), was altered by exercise in either
sham-operated or ORX rats. However, decreases in the phosphorylated Thr(17) form of PLB and the phosphorylated Thr(287) form of Ca(2+)/
calmodulin-dependent
kinase II in the hearts of ORX rats were abolished after regular exercise. These results thus support the use of regular running as a cardioprotective alternative to
testosterone replacement in hypogonadal conditions.