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

Abstract:

OBJECTIVE: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. DESIGN:Randomised, controlled study. SETTING:University research laboratory. SUBJECTS:One hundred and eleven male Wistar rats. INTERVENTION: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. MEASUREMENTS AND RESULTS: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. 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 associated with reduced GH receptor numbers.

journal_name

Intensive Care Med

journal_title

Intensive care medicine

authors

O'Leary MJ,Quinton N,Ferguson CN,Preedy VR,Ross RJ,Hinds CJ

doi

10.1007/s001340000656

keywords:

subject

Has Abstract

pub_date

2000-10-01 00:00:00

pages

1547-52

issue

10

eissn

0342-4642

issn

1432-1238

journal_volume

26

pub_type

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