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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

Departments of Diabetes and Endocrinology (M.G.G., N.J., F.S.-M., P.H.S., A.M.U.) and Elderly Care and Acute Medicine (F.C.M.), Division of Medicine King’s College London, St. Thomas’s Hospital London, London, United Kingdom SE1 7EH; and Division of Endocrinology (K.S.N.), Mayo Clinic College of Medicine, Rochester, Minnesota 55905

Address all correspondence and requests for reprints to: Margot Umpleby, Diabetes and Endocrinology, Postgraduate Medical School University of Surrey, Daphne Jackson Road, Manor Park Guildford GU2 7WG, United Kingdom. E-mail: m.umpleby{at}surrey.ac.uk.

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.