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This version published online on May 13, 2008
Journal of Clinical Endocrinology & Metabolism, doi:10.1210/jc.2007-2695
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Submitted on December 6, 2007
Accepted on May 2, 2008

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

Manthos G. Giannoulis M.D., Nicola Jackson Ph.D., Fariba Shojaee-Moradie Ph.D., K S Nair MD, Peter H. Sonksen M.D., Finbarr Martin M.D., and A Margot Umpleby Ph.D.*

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.


Key words: protein turnover • skeletal muscle • gene expression profile • leucine kinetics • Growth Hormone • Testosterone • IGF-I • elderly







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