Submitted to: American Journal of Physiology - Endocrinology and Metabolism
Publication Type: Peer reviewed journal
Publication Acceptance Date: 7/30/2008
Publication Date: 8/5/2008
Publication URL: ajpendo.physiology.org/cgi/reprint/295/4/E876
Citation: Wilson, F.A., Suryawan, A., Orellana, R.A., Nguyen, H.V., Jeyapalan, A.S., Gazzaneo, M.C., Davis, T.A. 2008. Fed levels of amino acids are required for the somatotropin-induced increase in muscle protein synthesis. American Journal of Physiology: Endocrinology and Metabolism. 295(4):E876-E883. Interpretive Summary: We have previously shown that administration of somatotropin, also known as growth hormone, increases the growth of skeletal muscle by increasing the synthesis of proteins in skeletal muscle and this effect is more prominent in the fed state. Somatotropin administration also increases the circulating concentration of the hormone insulin, which is a known promoter of the synthesis of skeletal muscle proteins. We have previously shown that the increase in muscle protein synthesis with somatotropin treatment in pigs is not due to the rise in the circulating concentration of insulin. To determine whether fed levels of amino acids are required for the stimulation of protein synthesis by somatotropin, we used a special technique, which we developed, to allow us to control the circulating levels of hormones, such as insulin, glucose, and amino acids in the blood, while we measured the synthesis of skeletal muscle proteins. We found that the stimulation of muscle protein synthesis by somatotropin treatment requires fed levels of amino acids, but not fed levels of insulin. We further found that the stimulation of protein synthesis by amino acids in animals treated with somatotropin does not involve the activation of intracellular signaling proteins that regulate mRNA translation. These studies are of importance to our understanding of the regulation of growth as well as to our development of a means to increase muscle mass in farm animals.
Technical Abstract: Chronic somatotropin (pST) treatment in pigs increases muscle protein synthesis and circulating insulin, a known promoter of protein synthesis. Previously, we showed that the pST-mediated rise in insulin could not account for the pST-induced increase in muscle protein synthesis when amino acids were maintained at fasting levels. This study aimed to determine whether the pST-induced increase in insulin promotes skeletal muscle protein synthesis when amino acids are provided at fed levels and whether the response is associated with enhanced translation initiation factor activation. Growing pigs were treated with pST (0 or 180 µg•kg(-1)•day(-1)) for 7 days, and then pancreatic-glucose-amino acid clamps were performed. Amino acids were raised to fed levels in the presence of either fasted or fed insulin concentrations; glucose was maintained at fasting throughout. Muscle protein synthesis was increased by pST treatment and by amino acids (with or without insulin) (P<0.001). In pST-treated pigs, fed but not fasting, amino acid concentrations further increased muscle protein synthesis rates irrespective of insulin level (P<0.02). Fed amino acids, with or without raised insulin concentrations, increased the phosphorylation of S6 kinase (S6K1) and eukaryotic initiation factor (eIF) 4E-binding protein 1 (4EBP1), decreased inactive 4EBP1•eIF4E complex association, and increased active eIF4E•eIF4G complex formation (P<0.02). pST treatment did not alter translation initiation factor activation. We conclude that the pST-induced stimulation of muscle protein synthesis requires fed amino acid levels, but not fed insulin levels. However, under the current conditions, the response to amino acids is not mediated by the activation of translation initiation factors that regulate mRNA binding to the ribosomal complex.