Apart from direct actions, including effects on genes regulating proliferation, myogenic differentiation, and muscle protein metabolism, indirect effects may explain at least part of the muscle hypertrophy observed following androgen administration. On the other hand, in another study, testosterone treatment failed to restore BC/LA weight following denervation , leaving open the possibility that androgens may also act upon motoneurons to affect muscle size. In addition, male mice with targeted AR overexpression in mesenchymal stem cells have reduced visceral and subcutaneous fat accumulation with a reciprocal increase in lean mass . In adult skeletal muscle, a population of uncommitted pluripotent progenitor cells of mesenchymal origin serves as a reservoir for the generation of new satellite cells during muscle regeneration or hypertrophy and of adipocytes . Therefore, the Bhasin group hypothesized that, in addition to direct effects on satellite cells, testosterone may promote the commitment of pluripotent precursor cells into the myogenic lineage and inhibit their differentiation into the adipogenic lineage . In patients suffering from androgen insensitivity syndrome (AIS) secondary to disrupted AR signaling, an increase in body fat is observed as well as a higher prevalence of obesity , suggesting that these androgen effects on body composition are mediated via the AR.
