Document Detail


Prednisolone reduces the ability of serum to activate the IGF1 receptor in vitro without affecting circulating total or free IGF1.
MedLine Citation:
PMID:  23038624     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: End-point bioassays based on thymidine or sulfate incorporation have demonstrated that glucocorticoid (GC) treatment inhibits serum IGF1 action, but the mechanism is unknown as serum IGF1 concentrations have been reported to either increase or remain unchanged.
AIM: To investigate whether GC treatment affects the ability of serum to activate the IGF1 receptor (IGF1R) in vitro (i.e. bioactive IGF1), using a specific cell-based IGF1 kinase receptor activation assay.
SUBJECTS AND METHODS: Twenty children with stable asthma (age 7.7-13.8 years) treated for 1 week with 5 mg prednisolone in a randomized, double-blind, placebo-controlled crossover study. Non-fasting serum samples were collected in the afternoon after each 7-day period and assayed for bioactive IGF1, free IGF1, total IGFs, IGF-binding proteins (IGFBPs), and insulin.
RESULTS: Prednisolone treatment reduced IGF1 bioactivity by 12.6% from 2.22±0.18 to 1.94±0.15 μg/l (P=0.01) compared with placebo. In contrast, no changes were observed for (μg/l; placebo vs prednisolone) total IGF1 (215±27 vs 212±24), free IGF1 (1.50±0.16 vs 1.43±0.17), total IGF2 (815±26 vs 800±31), IGFBP3 (3140±101 vs 3107±95), IGFBP2 (238±21 vs 220±19), IGFBP1 (32±6 vs 42±10), or IGFBP1-bound IGF1 (24±5 vs 26±7). Insulin remained unchanged as did IGFBP levels as estimated by western ligand blotting. Prednisolone had no direct effects on IGF1R phosphorylation.
CONCLUSIONS: Our study gives evidence that GC treatment induces a circulating substance that is able to inhibit IGF1R activation in vitro without affecting circulating free or total IGF1. This may be one of the mechanisms by which GC inhibits IGF1 action in vivo. However, the nature of this circulating substance remains to be identified.
Authors:
Jan Frystyk; Anders J Schou; Carsten Heuck; Henrik Vorum; Mikkel Lyngholm; Allan Flyvbjerg; Ole D Wolthers
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Publication Detail:
Type:  Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't     Date:  2012-12-10
Journal Detail:
Title:  European journal of endocrinology / European Federation of Endocrine Societies     Volume:  168     ISSN:  1479-683X     ISO Abbreviation:  Eur. J. Endocrinol.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2012-12-11     Completed Date:  2013-02-04     Revised Date:  2013-05-08    
Medline Journal Info:
Nlm Unique ID:  9423848     Medline TA:  Eur J Endocrinol     Country:  England    
Other Details:
Languages:  eng     Pagination:  1-8     Citation Subset:  IM    
Affiliation:
Institute of Clinical Medicine, Aarhus University, Aarhus C, Denmark. jan@frystyk.dk
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Asthma / drug therapy
Child
Cross-Over Studies
Female
Humans
Insulin-Like Growth Factor Binding Protein 1 / metabolism
Insulin-Like Growth Factor Binding Protein 2 / blood
Insulin-Like Growth Factor I / metabolism*
Male
Placebos
Prednisolone / pharmacology*,  therapeutic use
Receptor, IGF Type 1 / antagonists & inhibitors,  drug effects,  metabolism*
Chemical
Reg. No./Substance:
0/Insulin-Like Growth Factor Binding Protein 1; 0/Insulin-Like Growth Factor Binding Protein 2; 0/Placebos; 50-24-8/Prednisolone; 67763-96-6/Insulin-Like Growth Factor I; EC 2.7.10.1/Receptor, IGF Type 1

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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