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.
BACKGROUND
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.


METHODS
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).


METHODS
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).


CONCLUSIONS
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.
Giannoulis
Manthos G
MG
Department of Diabetes and Endocrinology, Division of Medicine King's College London, St. Thomas's Hospital London, London, UK.
Jackson
Nicola
N
Shojaee-Moradie
Fariba
F
Nair
K Sreekumaran
KS
Sonksen
Peter H
PH
Martin
Finbarr C
FC
Umpleby
A Margot
AM
D000368:Aged; D004311:Double-Blind Method; D015870:Gene Expression; D019382:Human Growth Hormone / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D053580:Muscle Strength; D018482:Muscle, Skeletal / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects; D011506:Proteins / Q000378:metabolism*; D013739:Testosterone / Q000627:therapeutic use*
D011506:Proteins; D019382:Human Growth Hormone; D013739:Testosterone