Growth hormone increases vascular cell adhesion molecule 1 expression: in vivo and in vitro evidence.
We investigated the impact of GH administration on endothelial adhesion molecules, vascular cell adhesion molecule-1 (VCAM-1) and E-selectin, in vivo and in vitro. Soluble VCAM-1, E-selectin, and C-reactive protein concentrations were measured before and after treatment in 25 healthy subjects and 25 adult GH-deficient (GHD) patients randomized to GH treatment or placebo. Furthermore, we studied the direct effect of GH and IGF-I and serum from GH-treated subjects on basal and TNF alpha-stimulated expression of VCAM-1 and E-selectin on cultured human umbilical vein endothelial cells. Baseline levels of VCAM-1, but not E-selectin, were significantly lower in GHD patients than in healthy subjects (362 +/- 15 microg/liter vs. 516 +/- 21 microg/liter, P < 0.001) and increased in GHD patients during GH treatment, compared with placebo [net difference between groups 151.8 microg/liter (95% confidence interval: 95.0-208.7 microg/liter); P < 0.0001]. In human umbilical vein endothelial cells, there was no direct stimulatory effect of either GH or IGF-I on the expression of VCAM-1 and E-selectin, but serum from GH-treated healthy subjects significantly increased the expression of VCAM-1 (P < 0.01). Our findings are compatible with the notion that GH may stimulate the expression of VCAM-1 indirectly through modulation of circulating factors. VCAM-1-mediated leukocyte extravasation is implicated in several illnesses including atherosclerosis and multiple-organ failure in sepsis, and we hypothesize that enhanced expression of VCAM-1 may contribute to the detrimental effects of GH in critically ill patients.
Hansen
Troels Krarup
TK
Immunoendocrine Research Unit , Medical Department M (Endocrinology and Diabetes), University Hospital of Aarhus, Kommunehospitalet, DK-8000 Aarhus C, Denmark. tkh@dadlnet.dk
Fisker
Sanne
S
Dall
Rolf
R
Ledet
Thomas
T
Jørgensen
Jens Otto L
JO
Rasmussen
Lars Melholt
LM
D002097:C-Reactive Protein / Q000378:metabolism; D016022:Case-Control Studies; D002478:Cells, Cultured; D019040:E-Selectin / Q000097:blood / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D005260:Female; D013006:Growth Hormone / Q000627:therapeutic use*; D019382:Human Growth Hormone / Q000172:deficiency*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D008661:Metabolism, Inborn Errors / Q000097:blood / Q000188:drug therapy / Q000378:metabolism; D009994:Osmolar Concentration; D014471:Umbilical Veins / Q000166:cytology / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood* / Q000378:metabolism
D019040:E-Selectin; D019010:Vascular Cell Adhesion Molecule-1; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D002097:C-Reactive Protein