Testosterone Supplementation Does Not Affect Skeletal Muscle Growth When Administered Alone in Either Sex and Requires an Additional Anabolic Stimulus to Exert Its Effects in Female Mice

Testosterone (T), the main androgenic hormone, is thought to positively affect skeletal muscle mass and function. The anabolic effects of T have been attributed to its effects on satellite cell proliferation and differentiation as well as its activation of pathways downstream of the IGF‐1 receptor and AKT. The role of T activity in skeletal muscle health and growth however remains equivocal, with some studies showing T to have great importance in muscle hypertrophy, while others suggest a limited role or no significant effect. Considering the increased use of chemical castration as a treatment for prostate cancer, and the growing use of testosterone in the elderly population, there is a growing need to establish T's role on skeletal muscle in relation to sex and age. Therefore, the aim of this project is to delineate molecular pathways that are affected by T as well as the phenotypic outcome of T treatment in skeletal muscle. The effects of supra‐physiological levels of T, in the form of subcutaneously implanted slow‐release T pellets, on muscle mass and strength were determined in 5‐month‐old male and female C57Bl6 mice. Mice were subjected to 3‐weeks of treatment and analyzed for muscle mass, plantar‐flexor strength, protein synthesis and degradation, and mTORC activity. Under free living conditions, T supplementation has no effect on mass of the TA, gastrocnemius, or quadriceps muscles in either sex; nor did it result in a gain in ankle extensor torque. In addition, T supplementation resulted in no significant changes in proteasome activity or whole muscle protein synthesis. To determine whether T has a greater effect on skeletal muscle mass when combined with increased load, we utilized the functional overload (FO) model, removing both the gastrocnemius and soleus muscles, in both sexes. Female mice that underwent FO and were supplemented with T for two weeks showed 94.6% ± 12.2% greater hypertrophy in the plantaris muscle compared to those that were not supplemented. However, in male mice T supplementation in addition to FO failed to significantly increase the plantaris mass when compared to those that only underwent FO. Fiber cross sectional area analysis of the investigated muscles compliments these phenotypic results. Together these data suggest that an additional and concurrent stimulus may be required for T to exert an anabolic effect in skeletal muscle of female mice. Additionally, T supplementation to male mice does not provide a beneficial effect when administered alone or together with increased load. Support or Funding Information UC Davis Clinical and Translational Science Center This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .