Responsiveness of muscle protein synthesis to growth hormone administration in HIV-infected individuals declines with severity of disease.
This study was undertaken to determine if human recombinant growth hormone (hrGH, 6 mg/d for 2 wk) would stimulate muscle protein synthesis in AIDS wasting. Healthy controls were compared with patients who were HIV+, had AIDS without weight loss, and had AIDS with > 10% weight loss. Before hrGH, rates of skeletal muscle protein synthesis, measured with l-[2H5]phenylalanine, were the same in controls and in all stages of disease. Rates of myofibrillar protein degradation, however, assessed from urinary excretion of 3-methyl histidine, were higher in AIDS and AIDS wasting than in HIV+ or healthy individuals. The group with weight loss had significantly higher TNFalpha levels but not higher HIV viral loads. Muscle function, as determined by isokinetic knee extension and shoulder flexion, was significantly higher in controls than all infected individuals. After GH, rates of protein synthesis were stimulated 27% in controls, with a smaller increase (11%) in HIV+, and a significant depression (42%) in AIDS with weight loss, despite fourfold elevation in insulin-like growth factor-I in all groups. There was a significant correlation of hrGH-induced changes in muscle protein synthesis with severity of disease (P = 0.002). The results indicate increased basal muscle protein degradation and decreased responsiveness of muscle protein synthesis to GH in the later stages of disease.
McNurlan
M A
MA
Department of Surgery, State University of New York at Stony Brook, Stony Brook, New York 11794, USA. mcnurlan@surg.som.sunysb.edu
Garlick
P J
PJ
Steigbigel
R T
RT
DeCristofaro
K A
KA
Frost
R A
RA
Lang
C H
CH
Johnson
R W
RW
Santasier
A M
AM
Cabahug
C J
CJ
Fuhrer
J
J
Gelato
M C
MC
D000328:Adult; D001481:Basal Metabolism; D018450:Disease Progression; D004351:Drug Resistance; D005260:Female; D019247:HIV Wasting Syndrome / Q000188:drug therapy*; D019382:Human Growth Hormone / Q000627:therapeutic use*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D008297:Male; D008762:Methylhistidines / Q000652:urine; D009119:Muscle Contraction / Q000502:physiology; D009124:Muscle Proteins / Q000096:biosynthesis*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D009210:Myofibrils / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D019562:Viral Load; D015430:Weight Gain / Q000187:drug effects
D008762:Methylhistidines; D009124:Muscle Proteins; D014409:Tumor Necrosis Factor-alpha; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; C028118:3-methylhistidine