Abstract
Testosterone (T), the main androgenic hormone, is assumed to play an important role in the maintenance of skeletal muscle mass and function through its effects on satellite cell proliferation and differentiation, as well as its activation of pathways downstream of the IGF‐1 receptor and AKT. T depletion through chemical castration as a treatment for prostate cancer and the use of T to treat sarcopenia are both common practices in older humans, yet the majority of animal studies aimed at elucidating T's role in the maintenance of skeletal muscle mass are performed in young rodents under the age of 3 months. In addition, the role of T's activity in skeletal muscle health remains equivocal, with some studies showing circulating T to have great importance, while others suggest a limited or non‐significant role. Hence, the aim of this project was to characterize the phenotypic outcome of T depletion on skeletal muscle across lifespan and identify the contributing molecular pathways.
To elucidate T's role on skeletal muscle throughout life, C57Bl/6 male mice were castrated at 4 different ages (1.5, 5, 12, or 24 months) and returned to normal cage activity for one month before muscle mass, protein synthesis and degradation, mTORC activity, and fiber cross sectional area were analyzed. Consistent with current literature, skeletal muscle mass reached a peak at 6 months before progressively declining (11.4% and 23.1% in the TA and gastrocnemius muscles, respectively) by 25‐months of age. In young animals, the removal of circulating T resulted in a decrease of the TA muscle mass (12.2% and 16.7% in the 1.5‐ and 5‐month old groups, respectively). Castration also slowed the growth of the gastrocnemius muscle with the 1.5‐ and 5‐month groups presenting muscles that are 9.4% and 11.6% smaller, respectively. Conversely, T depletion had no effect on muscle mass in the 12 months and 24 months groups. The decrease in cross sectional area in the absence of T in the young groups was similar to the decrease in muscle mass. Statistical analysis revealed a stronger interaction between age and treatment in the TA (P = 0.011) compared to the Gastrocnemius (P = 0.24). Together these data suggest that in skeletally immature animals, circulating T plays an important role in the regulation of muscle mass. In contrast, once muscle mass peaks and begins to decline naturally, circulating T no longer appears to affect muscle mass. Since T primarily affects skeletal maturation, it is essential that age appropriate animals are used when determining the role of T on skeletal muscle function. Specifically, studies on the anabolic effects of T need to use C57Bl/6 mice that are older than 6 months in order to translate to humans.
Support or Funding Information
UC Davis Clinical and Translational Science Center
UC Davis Office of Graduate Studies
This is from the Experimental Biology 2019 Meeting. There is no full text article associated with this published in The FASEB Journal.