Testosterone modulates the expression of the growth factor myostatin during myogenic differentiation and training induced skeletal muscle adaptation

The process of muscle adaptation is controlled and modulated by growth factors like Myostatin (MSTN) but also by male sex steroids. To investigate effects of testosterone on MSTN expression during myogenic differentiation and training induced skeletal muscle adaptation we performed different studies. In vitro C2C12 myoblastoma cells were treated with dihydrotestosterone (DHT), differentiation serum (DS), and DS + DHT. In vivo orchiectomised (ORX) and intact (INT) rats were treated with different doses of testosterone propionat (TP) and absolved a swim training over three days. Treated but untrained animals served as control group. MSTN mRNA levels were determined using quantitative real time RT-PCR.

In C2C12 cells an application of DS + DHT results in a stimulation of MSTN expression. Analysis of CK expression revealed that increase of MSTN expression correlates with an induction of differentiation. In vivo MSTN expression was downregulated in intact trained animals and in intact trained animals treated with TP. Treatment with TP in absence of training does not effect MSTN expression. In ORX rats training resulted in a dramatic up-regulation of MSTN expression, interestingly this effect could be antagonized by TP. Treatment with TP in absence of training resulted in significant stimulation of MSTN expression.

In summary our results clearly demonstrate that TP alters the expression of MSTN in vivo and in vitro. Interestingly, a modulation of MSTN mRNA expression in INT rats could only be observed when treatment was combined with training. These results can be taken as a hind that molecular mechanisms of the anabolic action of testosterone include a modulation of MSTN expression. Our in vitro results implicate a function during satellite cell differentiation. The observation that training in the absence of TP results in an enormous increase of MSTN expression, a growth factor known to inhibit skeletal muscle growth, may have implications with respect to the phenomena of age related loss of muscle mass (sarcopenia) what has to be investigated in future studies.