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

Objective: Growth hormone (GH) given to reverse muscle catabolism in critic al illness increased mortality, illustrating the need for better understand ing of the pathophysiology of the GH axis. We describe the relationship bet ween changes in plasma insulin-like growth factor-I (IGF-I) and growth horm one-binding protein (GHBP) levels and hepatic growth hormone-binding in rat s with sepsis. Design: Randomised, controlled study. Setting: University re search laboratory. Subjects: One hundred and eleven male Wistar rats. Inter vention: Three groups of rats underwent caecal ligation and puncture (CLP) and three groups laparotomy only (LAP). Survivors were killed at 24, 72, an d 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 . Measurements and results: Plasma levels of IGF-I and GHBP and binding of I-125-labelled human GH in liver homogenates were measured. IGF-I fell sign ificantly following both CLP and LAP; at 24 h, IGF-I levels were lower afte r CLP than LAP (950 +/- 74 vs 1522 +/- 60 mug/l, P = < 0.001). GHBP increas ed at 24 h following both CLP and LAP (45.6 +/- 1.87 and 47.7 +/- 3.01 vs 3 8.7 +/- 1.98 ng/ml at baseline, P = < 0.05). In LAP animals GHBP fell to be low 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 baselin e by 96 h. The density of GH-binding sites in liver tended to increase, fol lowing both CLP and LAP at both 24 and 96 h, but these changes failed to ac hieve statistical significance. Conclusion: 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 ass ociated with reduced GH receptor numbers.