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Submitted on December 6, 2007
Accepted on May 2, 2008
Department of Diabetes & Endocrinology (M.G.G., N.J., F.S.M., P.H.S., M.U.), and Elderly Care & Acute Medicine (F.M.), Division of Medicine King's College London, St. Thomas's Hospital, London, United Kingdom SE1 7E; and Division of Endocrinology, Mayo Clinic College of Medicine, Rochester, MN, USA (S.N.)
* To whom correspondence should be addressed. E-mail: umpleby{at}surrey.ac.uk.
Context: Alterations of protein turnover may contribute to the progressive decline of muscle mass with ageing.
Objective: The effects of near physiological recombinant growth hormone (GH) and /or testosterone (T) administration to older men on whole body protein kinetics (WBPK) and muscle gene expression.
Design, settings, and participants: A six months randomised, double blind, placebo controlled trial in twenty one healthy elderly men aged 65 to 75 years. Participants were randomised to receive placebo GH and placebo T (P), GH and placebo T (GH), T and placebo GH (T) or GH and T (GHT).
Interventions: Leucine rate of appearance (Ra, index of proteolysis), non-oxidative leucine disposal Rd (NOLD, 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, body composition and aerobic capacity (VO2max).
Results: Serum IGF-I levels increased significantly with GH and GHT (P < 0.001) compared to placebo. T increased significantly only in the T group (P = 0.028). Leucine Ra and NOLD 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. Mid thigh muscle mass and VO2max 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 months 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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