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 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.


METHODS
Randomised, controlled study.


METHODS
University research laboratory.


METHODS
One hundred and eleven male Wistar rats.


METHODS
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.


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.


CONCLUSIONS
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.
O'Leary
M J
MJ
Intensive Care Unit, The St George Hospital, Kogarah, NSW, Australia. m.oleary@unsw.edu.au
Quinton
N
N
Ferguson
C N
CN
Preedy
V R
VR
Ross
R J
RJ
Hinds
C J
CJ
D000818:Animals; D002352:Carrier Proteins / Q000097:blood*; D002432:Cecum / Q000601:surgery; D016638:Critical Illness; D004195:Disease Models, Animal; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000032:analysis / Q000378:metabolism*; D007813:Laparotomy; D008026:Ligation; D008099:Liver / Q000737:chemistry; D008297:Male; D011677:Punctures; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D018805:Sepsis / Q000097:blood*; D013217:Starvation / Q000378:metabolism; D013997:Time Factors
D002352:Carrier Proteins; D007334:Insulin-Like Growth Factor I; C051815:somatotropin-binding protein