Regulation of protein degradation in skeletal muscle.

Protein balance in rat muscles incubated in vitro is influenced by the supply of insulin, leucine and various hormones at physiological concentrations (0.1-0.5 mM) (Goldberg & Chang, 1978; Goldberg et al., 1980). Leucine, but no other amino acid, stimulates protein synthesis and inhibits protein breakdown in this tissue. Metabolism of leucine is necessary for its inhibitory effect on proteolysis but not for the stimulation of protein synthesis. Thyroid hormones promote both protein synthesis and stimulate breakdown. This acceleration of catabolism is responsible for the muscle wasting in hyperthyroidism. Co-ordinate with the effects of thyroid hormone or thyroidectomy on protein breakdown are changes in muscle content of lysosomal enzymes. The decline in thyroid function during long-term starvation may also account for the preservation of muscle protein and the retardation of proteolysis under these conditions. Inhibitors of lysosomal function retard protein breakdown (1540%) and have much more dramatic effects on the breakdown of certain cell components (e.g. the acetylcholine receptor). Treatment with such inhibitors of lysosomal function can retard atrophy of muscles in organ culture. On starvation, protein breakdown in muscle increases, and this effect requires the presence of glucocorticoids. In tissues of adrenalectomized animals, protein breakdown does not increase and may even decrease during starvation. These hormones increase protein breakdown and promote the release of amino acids from muscles of starved but not from those of fed animals. The ability of glucocorticoids to promote protein breakdown in muscle during starvation complements their actions in stimulating hepatic gluconeogenesis from amino acids.