Human growth hormone increases vascular cell adhesion molecule 1 expression: in vivo and in vitro evidence.
Hansen TK - J Clin Endocrinol Metab - 01-FEB-2004; 89(2): 909-16
From NIH/NLM MEDLINE
NLM Citation ID:
14764813 (PubMed)
Full Source Title:
Journal of Clinical Endocrinology and Metabolism
Publication Type:
Clinical Trial; Journal Article; Randomized Controlled Trial
Language:
English
Author Affiliation:
Immunoendocrine Research Unit , Medical Department M (Endocrinology and Diabetes), University Hospital of Aarhus, Kommunehospitalet, DK-8000 Aarhus C, Denmark. tkh@dadlnet.dk
Authors:
Hansen TK; Fisker S; Dall R; Ledet T; Jørgensen JO; Rasmussen LM
Abstract:
We investigated the impact of HGH 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 HGH-deficient (HGHD) patients randomized to HGH treatment or placebo. Furthermore, we studied the direct effect of HGH and IGF-I and serum from HGH-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 HGHD patients than in healthy subjects (362 +/- 15 microg/liter vs. 516 +/- 21 microg/liter, P < 0.001) and increased in HGHD 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 HGH-treated healthy subjects significantly increased the expression of VCAM-1 (P < 0.01). Our findings are compatible with the notion that HGH 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 HGH in critically ill patients.
Major Subjects:
- Growth Hormone / * therapeutic use
- Human Growth Hormone / * deficiency
- Vascular Cell Adhesion Molecule-1 / * blood / metabolism
Additional Subjects:
- C-Reactive Protein / metabolism
- Case-Control Studies
- Cells, Cultured
- E-Selectin / blood / metabolism
- Endothelium, Vascular / cytology / metabolism
- Female
- Humans
- Insulin-Like Growth Factor I / metabolism
- Male
- Metabolism, Inborn Errors / blood / drug therapy / metabolism
- Osmolar Concentration
- Research Support, Non-U.S. Gov't
- Umbilical Veins / cytology / metabolism
Chemical Compound Name:
(E-Selectin); (Vascular Cell Adhesion Molecule-1); 12629-01-5(Human Growth Hormone); 67763-96-6(Insulin-Like Growth Factor I); 9002-72-6(Growth Hormone); 9007-41-4(C-Reactive Protein)