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Glucocorticoid excess induces preferential depletion of myosin in denervated skeletal muscle fibers

The combined effects of dexamethasone treatment (1 mg/Kg/day) plus denervation (DEX‐DEN), were studied at 7, 13, and 28 days by microscopic, biochemical, and physiological techniques in plantaris and soleus muscles of adult rats. The results were compared with corresponding dexamethasone‐treated (DEX) and denervated (DEN) muscles and appropriate controls. There was a significantly more marked atrophy of all fiber types in the DEX‐DEN plantares at 7 and 13 days than in either DEX or DEN muscles. The degree of atrophy was greatest in type 2B fibers in DEX‐DEN plantares. Electron microscopy revealed a severe preferential depletion of thick myofilaments in DEX‐DEN plantares and solei but not in DEX or DEN muscles. The thick myofilament depletion in DEX‐DEN muscles occurred in addition to a severe overall reduction of myofibrillar caliber. Gel electrophoresis showed a marked preferential decrease of myosin heavy chain in DEX‐DEN plantares and solei, but not in either DEX or DEN muscles. Myosin light chains were also markedly reduced in DEX‐DEN plantares and solei. In vitro physiological studies showed a marked reduction of the denervation‐induced twitch potentiation in DEX‐DEN solei. Maximal tetanic tension (20 Hz stimulation) per gram weight of muscle as well as the twitch‐tetanus ration was significantly reduced only in DEX‐DEN solei in relation to controls. Myosin depletion in DEX‐DEN muscles may be due to a severe preferential inhibition of its synthesis coupled with an accelerated catabolism.