In rats with sepsis, the acute fall in IGF-I is associated with an increase in circulating growth hormone-binding protein levels

• Published in: Intensive care medicine 2000-10, Vol.26 (10), p.1547-1552
• Main Authors: O'LEARY, M. J, QUINTON, N, FERGUSON, C. N, PREEDY, V. R, ROSS, R. J M, HINDS, C. J
• Format: Article
• Language: English
• Subjects: Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Animals; Biological and medical sciences; Carrier Proteins - blood; Cecum - surgery; Critical Illness; Disease Models, Animal; Emergency and intensive care: infection, septic shock; Food; Growth hormone; Growth hormones; Humans; Insulin-like growth factor I; Insulin-Like Growth Factor I - analysis; Insulin-Like Growth Factor I - metabolism; Intensive care medicine; Laparotomy; Ligation; Liver; Liver - chemistry; Male; Medical sciences; Mortality; Muscles; Plasma levels; Punctures; Random Allocation; Rats; Rats, Wistar; Sepsis; Sepsis - blood; Starvation - metabolism; Statistics; Time Factors
• ISSN: 0342-4642; 1432-1238
• DOI: 10.1007/s001340000656

Growth hormone (GH) given to reverse muscle catabolism in critical illness increased mortality, illustrating the need for better understanding of the pathophysiology of the GH axis. We describe the relationship between changes in plasma insulin-like growth factor-I (IGF-I) and growth hormone-binding protein (GHBP) levels and hepatic growth hormone-binding in rats with sepsis. Randomised, controlled study. University research laboratory. One hundred and eleven male Wistar rats. Three groups of rats underwent caecal ligation and puncture (CLP) and three groups laparotomy only (LAP). Survivors were killed at 24, 72, and 96 h. All animals were starved during the study. Twelve rats were killed at the start of the experiment (baseline) and twelve (allowed food) at 96 h. Plasma levels of IGF-I and GHBP and binding of 125I-labelled human GH in liver homogenates were measured. IGF-I fell significantly following both CLP and LAP; at 24 h, IGF-I levels were lower after CLP than LAP (950 +/- 74 vs 1,522 +/- 60 microg/l, P = < 0.001). GHBP increased at 24 h following both CLP and LAP (45.6 +/- 1.87 and 47.7 +/- 3.01 vs 38.7 +/- 1.98 ng/ml at baseline, P = < 0.05). In LAP animals GHBP fell to below baseline by 72 h, and significantly so by 96 h (33.5 +/- 1.43, P = < 0.05), whereas GHBP remained elevated 72 h following CLP, returning to baseline by 96 h. The density of GH-binding sites in liver tended to increase, following both CLP and LAP at both 24 and 96 h, but these changes failed to achieve statistical significance. Reduced IGF-I levels in sepsis in the rat are associated with elevations in GHBP and a trend to increased hepatic GH binding. This suggests that in sepsis 'GH resistance' is not associated with reduced GH receptor numbers.