Effects of testosterone replacement therapy on skeletal muscle after spinal cord injury

Abstract

Patients with spinal cord injury (SCI) are at risk for developing several secondary pathologies likely linked to the atrophy of affected muscle. If testosterone replacement therapy (TRT) alone or as an adjunct therapy could attenuate the atrophy, these risks might be reduced. Therefore, the purpose of this study is to examine the effects of TRT on rat skeletal muscle after SCI and determine the applicability of the rat model to studies of skeletal muscle unweighting. In addition, the applicability of rat models in unweighting studies will be tested by quantifying the characteristics of anatomically similar muscles in rat and human, control and SCI muscles. The soleus, gastrocnemius, tibialis anterior, vastus lateralis and triceps brachii were taken from twelve male Charles River rats 11 weeks after complete SCI (n = 8) or sham surgery (n =4) and analyzed qualitatively for type and quantitatively for succinate dehydrogenase (SDH), a -glycerol-phosphate dehydrogenase (GPDH), and actomyosin ATPase (qATPase). Rats received either testosterone or empty capsule implantation at the time of surgery. Overall, SCI resulted in a smaller fiber size, a decrease in SDH, and an increase in GPDH activity, while the triceps brachii increased fiber size with no change in SDH or GPDH activity. Rats had smaller fibers, greater SDH and GPDH activities, an absence of slow fibers and a greater proportion of IIb/x fibers compared to humans. The reduction in SDH activity was greater in rats while atrophy and IIa .IIb/x fiber shift occurred to a greater extent in humans. TRT after SCI attenuated the fiber atrophy and the changes in SDH and GPDH activities. There was no effect of TRT on the TRI relative to SCI alone, nor on the qATPase activity in rat or human SCI or TRT treated muscles. Thus, it is suggested that the rat is a reasonable model for studying the predominant response to SCI, atrophy. However, its high proportion of IIb/x fibers limits evaluation of the mechanical consequences of shifting to "faster" contractile machinery after SCI. It is also concluded that TRT was effective in attenuating alterations in myofibrillar proteins in affected skeletal muscles after SCI.