The role of proteases in experimental glucocorticoid myopathy

Mature, male, New Zealand white rabbits were treated with the synthetic glucocorticoid betamethasone (0.3 mg/kg body weight/day) for 2 weeks. The glucocorticoid treatment caused a 30% decrease in muscle weight of the type 2 psoas muscle, but had no apparent effect on the type 1 soleus muscle. Cathepsin D activity was elevated twofold in the psoas muscle of treated rabbits, a finding suggesting an active role for lysosomes in mediating muscle breakdown in glucocorticoid-induced myopathy of the rabbit. There was no detectable alkaline serine protease activity in the muscles from either treated or control rabbits. Alkaline protease is localized in mast cells in some species, particularly the rat. Toluidine blue staining for mast cells was absent in rabbit muscles, a finding indicating that this species does not contain these cells. This protease, previously implicated in glucocorticoid myopathy, apparently plays no role in rabbit myopathy. There was no detectable elevation of the Ca-activated protease in muscles from glucocorticoid-treated animals. This finding suggests that if this protease plays a role in muscle degradation, its activity is controlled in vivo by special conditions (such as elevated CA levels, inhibitors, and compartmentalizations).