title: Prednisolone reduces the ability of serum to activate the IGF1 receptor in vitro without affecting circulating total or free IGF1.
abstract: 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.
  
  
  OBJECTIVE
  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.
  
  
  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.affiliation: Institute of Clinical Medicine, Aarhus University, Aarhus C, Denmark. jan@frystyk.dk
authors.forename: Jan
authors.initials: J
authors.lastname: Frystyk
authors.forename: Anders J
authors.initials: AJ
authors.lastname: Schou
authors.forename: Carsten
authors.initials: C
authors.lastname: Heuck
authors.forename: Henrik
authors.initials: H
authors.lastname: Vorum
authors.forename: Mikkel
authors.initials: M
authors.lastname: Lyngholm
authors.forename: Allan
authors.initials: A
authors.lastname: Flyvbjerg
authors.forename: Ole D
authors.initials: OD
authors.lastname: Wolthers
mesh_terms: D000293:Adolescent; D001249:Asthma / Q000188:drug therapy; D002648:Child; D018592:Cross-Over Studies; D005260:Female; D006801:Humans; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000378:metabolism; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008297:Male; D010919:Placebos; D011239:Prednisolone / Q000494:pharmacology* / Q000627:therapeutic use; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism*
chemical_list: D018970:Insulin-Like Growth Factor Binding Protein 1; D018971:Insulin-Like Growth Factor Binding Protein 2; D010919:Placebos; D007334:Insulin-Like Growth Factor I; D011239:Prednisolone; D017526:Receptor, IGF Type 1