Submitted to: Endocrinology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/23/2002
Publication Date: 4/1/2003
Citation: Bush, J.A., Kimball, S.R., O'Connor, P.M., Suryawan, A., Orellana, R.A., Nguyen, H.V., Jefferson, L.S., Davis, T.A. 2003. Translational control of protein synthesis in muscle and liver of growth hormone-treated pigs. Journal of Endocrinology. 144(4):1273-1283. Interpretive Summary: Researchers are aware that growth hormone (GH) promotes the deposition of protein in the whole body. We recently found that GH treatment stimulated protein deposition in the hindlimb in the fed state. In this study, we wanted to determine the effect of GH treatment on protein synthesis in skeletal muscle in both the fed and fasted state, and to compare the results in the muscle to those in the liver. We also wanted to understand the mechanisms inside the cell that regulate this process. We treated piglets for 7 days with GH during the fed and fasted state. We found that GH treatment increased protein synthesis in skeletal muscle, but only in the fed state. We found that the mechanism by which this process worked was that GH promoted an increase in the activation of components of the signaling pathway, speeding up the activity of the protein synthetic machinery. This was associated with an increase in the activity of factors involved in the regulation of protein synthesis. In contrast to what happened in the muscle, GH treatment increased protein synthesis in the liver in both the fasted and fed states. This was associated with an increase in the number of ribosomes, so that there was an increase in amount but not the activity. That means GH promotes protein synthesis in different ways in different organs in the body, and uses different mechanisms to do it. This is useful information because it could ultimately affect the way that GH, as a drug, is administered to humans with growth problems, with respect to the different ways it affects different parts of their bodies under varying feeding conditions.
Technical Abstract: Growth hormone (GH) treatment increases protein deposition and the efficiency of dietary protein used for growth. To identify the mechanisms that regulate tissue protein synthesis in response to exogenous GH treatment, fully fed, growing swine were treated with GH for 7d. Fasted and fed pigs were infused with [1-13C]leucine to determine protein synthesis rates and translation initiation factor activity levels in skeletal muscle and liver. Feeding increased 4E-BP1 and S6K1 phosphorylation, decreased the association of eIF4E with 4E-BP1, and increased the association of eIF4E with eIF4G in both muscle and liver of control and GH-treated pigs. GH increased muscle protein synthesis and translational efficiency in fed pigs. GH increased liver protein synthesis of fasted and fed pigs in association with increased ribosome number. In muscle, but not liver, GH increased eIF2B activity and 4E-BP1 phosphorylation in both the fasted and fed state, and increased the association of eIF4E with eIF4G in the fed state. We conclude that GH increases muscle protein synthesis in the fed state, in part, via mechanisms that enhance the binding of mRNA and met-tRNAi to the 40S ribosomal subunit, while GH increases liver protein synthesis in the fasted and fed states by increasing ribosome number. The results further indicate that the GH-induced protein synthetic response is dependent upon nutritional state, and is tissue-specific.