Inactivity amplifies the catabolic response of skeletal muscle to cortisol

Severe injury or trauma is accompanied by both hypercortisolemia and prolon ged inactivity or bed rest (BR). Trauma and BR alone each result in a loss of muscle nitrogen, albeit through different metabolic alterations. Althoug h BR alone can result in a 2-3% loss of lean body mass, the effects of seve re trauma can be 2- to 3-fold greater. We investigated the combined effects of hypercortisolemia and prolonged inactivity on muscle protein metabolism in healthy volunteers. Six males were studied before and after 14 days of strict BR using a model based on arteriovenous sampling and muscle biopsy. Fractional synthesis and breakdown rates of skeletal muscle protein were al so directly calculated. Each assessment of protein metabolism was conducted during a 12-h infusion of hydrocortisone sodium succinate (120 mu g/kg.h), resulting in blood cortisol concentrations that mimic severe injury (appro ximate to 31 mu g/dL). After 14 days of strict BR, hypercortisolemia increa sed phenylalanine efflux from muscle by 3-fold (P < 0.05). The augmented ne gative amino acid balance was the result of an increased muscle protein bre akdown (P < 0.05) without a concomitant change in muscle protein synthesis. Muscle efflux of glutamine and alanine increased significantly after bed r est due to a significant increase in de novo synthesis (P < 0.05). Thus, in activity sensitizes skeletal muscle to the catabolic effects of hypercortis olemia. Furthermore, these effects on healthy volunteers are analogous to t hose seen after severe injury.