title: Translational control of protein synthesis in muscle and liver of growth hormone-treated pigs.
abstract: 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 7 d. Fasted and fed pigs were infused with [1-(13)C]leucine to determine protein synthesis rates, and translation initiation factor activity levels were measured in skeletal muscle and liver. Feeding increased protein synthesis and translational efficiency in both muscle and liver of control and GH-treated pigs, and this was associated with increased 4E-BP1 and S6 kinase 1 phosphorylation, decreased association of eukaryotic initiation factor (eIF) 4E with 4E-BP1, and increased association of eIF4E with eIF4G. 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 methionyl-tRNA to the 40S ribosomal subunit, whereas 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.
authors.affiliation: United States Department of Agriculture/Agricultural Research Service Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Jill A
authors.initials: JA
authors.lastname: Bush
authors.forename: Scot R
authors.initials: SR
authors.lastname: Kimball
authors.forename: Pamela M J
authors.initials: PM
authors.lastname: O'Connor
authors.forename: Agus
authors.initials: A
authors.lastname: Suryawan
authors.forename: Renan A
authors.initials: RA
authors.lastname: Orellana
authors.forename: Hanh V
authors.initials: HV
authors.lastname: Nguyen
authors.forename: Leonard S
authors.initials: LS
authors.lastname: Jefferson
authors.forename: Teresa A
authors.initials: TA
authors.lastname: Davis
mesh_terms: D000818:Animals; D001786:Blood Glucose; D001835:Body Weight / Q000187:drug effects; D002352:Carrier Proteins / Q000378:metabolism; D004435:Eating; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism; D020717:Eukaryotic Initiation Factor-2B / Q000378:metabolism; D039561:Eukaryotic Initiation Factor-4E / Q000378:metabolism; D039603:Eukaryotic Initiation Factor-4G / Q000378:metabolism; D005215:Fasting; D005260:Female; D005934:Glucagon / Q000097:blood; D013006:Growth Hormone / Q000494:pharmacology*; D007328:Insulin / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008099:Liver / Q000502:physiology*; D018482:Muscle, Skeletal / Q000502:physiology*; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D014176:Protein Biosynthesis / Q000187:drug effects* / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D019893:Ribosomal Protein S6 Kinases / Q000378:metabolism; D034421:Sus scrofa
chemical_list: D001786:Blood Glucose; D002352:Carrier Proteins; D015852:Eukaryotic Initiation Factor-2; D020717:Eukaryotic Initiation Factor-2B; D039561:Eukaryotic Initiation Factor-4E; D039603:Eukaryotic Initiation Factor-4G; D007328:Insulin; D010750:Phosphoproteins; D011518:Proto-Oncogene Proteins; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D005934:Glucagon; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D019893:Ribosomal Protein S6 Kinases