The effects of growth hormone and/or testosterone on whole body protein kinetics and skeletal muscle gene expression in healthy elderly men: a randomized controlled trial

J Clin Endocrinol Metab. 2008 Aug;93(8):3066-74. doi: 10.1210/jc.2007-2695. Epub 2008 May 13.

Abstract

Context: Alterations of protein turnover may contribute to the progressive decline of muscle mass with aging.

Objective: Our objective was to examine the effects of near-physiological recombinant human GH and/or testosterone (T) administration to older men on whole body protein kinetics and muscle gene expression.

Design, settings, and participants: A 6-month randomized, double-blind, placebo-controlled trial in 21 healthy elderly men aged 65-75 yr, was performed. Participants were randomized to receive placebo GH and placebo T, rhGH and placebo T (GH), T and placebo GH (T), or rhGH and T (GHT).

Interventions: The leucine rate of appearance (index of proteolysis), nonoxidative leucine disposal rate (an index of protein synthesis), and leucine oxidation rate were measured with an infusion of l-[1-(13)C] leucine. Muscle biopsies for the measurement of gene expression were performed. Body composition and aerobic capacity (maximal oxygen capacity) were measured.

Results: Serum IGF-I levels increased significantly with GH and GHT (P < 0.001) compared with placebo. T increased significantly only in the T group (P = 0.028). Leucine rate of appearance and nonoxidative leucine disposal rate increased with GH (P = 0.015, P = 0.019) and GHT (P = 0.017, P = 0.02), but leucine oxidation did not change significantly in any treatment group. Midthigh muscle mass and maximal oxygen capacity increased (P < 0.04) with GHT only. Expression of muscle function genes did not change significantly, but the within-group comparisons revealed a significant increase of androgen receptor expression in the GHT group (P = 0.001).

Conclusion: This study showed that 6-month treatment with low-dose GH alone or with T in healthy elderly men produces comparable increments in whole body protein turnover and protein synthesis.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Double-Blind Method
  • Gene Expression
  • Human Growth Hormone / adverse effects
  • Human Growth Hormone / therapeutic use*
  • Humans
  • Male
  • Muscle Strength
  • Muscle, Skeletal / metabolism*
  • Oxygen Consumption / drug effects
  • Proteins / metabolism*
  • Testosterone / therapeutic use*

Substances

  • Proteins
  • Human Growth Hormone
  • Testosterone