Context: Though growth hormone (GH) promotes growth and protein anabolism, which are ATP-dependent processes, the GH effect on mitochondrial regulation remains to be determined.

Objective: To determine the acute effect of GH on mitochondrial oxidative capacity in skeletal muscle of healthy subjects

Design: A randomized crossover design was used.

Setting: Academic medical center.

Participants: Nine healthy men and women completed the study.

Intervention: GH (150µg/hr) or saline was infused for 14 h on separate days and muscle biopsies were obtained.

Main Outcome Measures: 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 (COX4) and mitochondrial (COX3) genomes, the nuclear-derived mitochondrial transcription factor A (TFAM), and glucose transporter 4. While GH increased whole body protein synthesis (non-oxidative 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 a 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.