Long term adrenal insufficiency induces skeletal muscle atrophy and increases the serum levels of active form myostatin in rat serum

Skeletal muscle wasting is a common symptom in the adrenal insufficiency such as Addison's disease. Although it has been suspected that several cytokines and/or growth factors are responsible for the manifestation of the symptom, the precise mechanisms underlying the phenomenon have so far been poorly understood. Myostatin is predominantly expressed in skeletal muscles and involved in the regulation of skeletal muscle mass. Recently, several reports indicated that myostatin is secreted into the circulation and the increased levels of circulating myostatin is associated with the induction of skeletal muscle wasting in adult animals. We, therefore, hypothesized that the increased levels of circulating myostatin may account for the development of skeletal muscle wasting in adrenal insufficiency. To test the validity of this hypothesis, we compared the serum levels of myostatin in normal with those in bilaterally adrenalectomized (ADX) rats, a model of Addison's disease, by Western blot analysis. The active form of myostatin (13 kDa) was barely detectable in the sera collected either 1 month or 2 month after adrenalectomy, but present at conspicuously detectable levels in those obtained 3 month after the operation, while the total amounts of myostatin proteins (sum of the precursor and the active forms) remained constant at all the time points examined post-operatively. These results are consistent with the hypothesis that the increased serum levels of active form of myostatin protein, induced yet unknown post-translational control mechanisms may be responsible, at least in part, for the muscle wasting associated with the adrenal insufficiency syndromes.