GLUTAMINE PREVENTS DOWN-REGULATION OF MYOSIN HEAVY-CHAIN SYNTHESIS AND MUSCLE ATROPHY FROM GLUCOCORTICOIDS

The aims of this study were to determine whether glutamine infusion pr events the decline in protein synthesis and muscle wasting associated with repeated glucocorticoid treatment. Hormone (cortisol acetate, 100 mg.kg body wt(-1).day(-1)) and vehicle (carboxymethyl cellulose)-trea ted female rats were infused with either saline or glutamine (240 mM, 0.75 ml/h) for a 7-day period. Glutamine infusion attenuated the decli ne of plantaris muscle glutamine concentration (3.0 +/- 0.2 vs. 2.3 +/ - 0.2 mu mol/g) and prevented > 70% of the total muscle mass losses du e to the glucocorticoid injections. Fractional synthesis rates of myos in heavy chain (MHC) and total protein were determined after constant [H-3]leucine infusion from the leucyl-tRNA precursor pool, which was s imilar in all groups (range 4.8 +/- 0.5 to 6.3 +/- 0.4 disintegrations min(-1).pmol(-1)). MHC synthesis rates (%/day) in plantaris muscles w ere reduced to similar to 40% of controls (4.2/9.4). Although glutamin e had no effect on MHC synthesis in vehicle-treated animals (10.1/9.4) , it prevented 50% (7.6/4.2) of the hormone-induced decline in MHC syn thesis rates. The same results were obtained with total protein synthe sis measurements. Changes in muscle mass did not appear related to-est imates of protein breakdown. In conclusion, these data show that gluta mine infusion is effective therapy in counteracting glucocorticoid-ind uced muscle atrophy. Atrophy attenuation appears related to maintainin g muscle glutamine levels, which in turn may limit the glucocorticoid- mediated downregulation of MHC synthesis.