TY - JOUR
T1 - The effects of growth hormone and/or testosterone on whole body protein kinetics and skeletal muscle gene expression in healthy elderly men
T2 - A randomized controlled trial
AU - Giannoulis, Manthos G.
AU - Jackson, Nicola
AU - Shojaee-Moradie, Fariba
AU - Nair, K. Sreekumaran
AU - Sonksen, Peter H.
AU - Martin, Finbarr C.
AU - Umpleby, A. Margot
PY - 2008/8
Y1 - 2008/8
N2 - 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-[1-13C] 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.
AB - 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-[1-13C] 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.
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U2 - 10.1210/jc.2007-2695
DO - 10.1210/jc.2007-2695
M3 - Article
C2 - 18477661
AN - SCOPUS:49249130045
SN - 0021-972X
VL - 93
SP - 3066
EP - 3074
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
IS - 8
ER -