Enhancement of muscle mitochondrial function by growth hormone

Kevin R. Short, Niels Moller, Maureen L. Bigelow, Jill Coenen-Schimke, K. Sreekumaran Nair

Research output: Contribution to journalArticle

59 Scopus citations

Abstract

Context: Although GH promotes growth and protein anabolism, which are ATP-dependent processes, the GH effect on mitochondrial regulation remains to be determined. Objective: Our objective was to determine the acute effect of GH on mitochondrial oxidative capacity in skeletal muscle of healthy subjects. Design and Setting: The study was a randomized crossover design at an academic medical center. Participants: Nine healthy men and women completed the study. Intervention: GH (150 μg/h) or saline was infused for 14 h on separate days, and muscle biopsies were obtained. Main Outcome Measures: Outcome measures included mitochondrial function, gene expression, and protein metabolism. Results: The 4-fold increase in plasma GH caused elevations in plasma IGF-I, insulin, glucose, and free fatty acids and a shift in fuel selection, with less carbohydrate (-69%) and leucine (-43%) oxidation and 29% more fat oxidation. Muscle mitochondrial ATP production rate and citrate synthase activity were increased 16-35% in response to GH. GH also resulted in higher abundance of muscle mRNAs encoding IGF-I, mitochondrial proteins from the nuclear (cytochrome c oxidase subunit 4) and mitochondrial (cytochrome c oxidase subunit 3) genomes, the nuclear-derived mitochondrial transcription factor A, and glucose transporter 4. Although GH increased whole-body protein synthesis (nonoxidative disposal of leucine), no effect on synthesis rate of muscle mitochondrial proteins was observed. Conclusions: These results demonstrate that acute GH action promotes an increase in mitochondrial oxidative capacity and abundance of several mitochondrial genes. These events may occur through direct or indirect effects of GH on intracellular signaling pathways but do not appear to involve a change in mitochondrial protein synthesis rate.

Original languageEnglish (US)
Pages (from-to)597-604
Number of pages8
JournalJournal of Clinical Endocrinology and Metabolism
Volume93
Issue number2
DOIs
StatePublished - Feb 2008

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

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