No influence of prednisolone on IGFBP-3 proteolysis in healthy young men.
OBJECTIVE
The impact of growth hormone (GH) and prednisolone on the GH/insulin-like growth factor (IGF) axis with special emphasis on IGF binding protein-3 (IGFBP-3) proteolysis was studied in 8 healthy adults in a double-blind cross-over study with four periods: (1) placebo; (2) s.c. GH 0.1 IU/kg/day; (3) oral prednisolone 50 mg/day, and (4) co-administration of GH and prednisolone.


METHODS
Each treatment period lasted for 4 days followed by a washout period of 10 days. We measured IGF-I, IGF-II, IGFBP-1, IGFBP-2, IGFBP-3 by immunoassays, IGFBP-3 by Western ligand blotting (WLB) and finally in vitro IGFBP-3 proteolysis by a (125)I-IGFBP-3 degradation assay.


RESULTS
IGF-I levels increased by 99% during GH administration and 67% during co-administration of GH and prednisolone (p < 0.0005), whereas no significant change was seen during prednisolone alone. IGFBP-1 levels decreased 55% during the prednisolone period (p < 0.002), but the between period changes were not significant (p < 0.1). IGFBP-2 decreased 33% during co-administration of GH and prednisolone (p < 0.002). IGFBP-3 increased 12% during GH and 7% during co-administration of GH and prednisolone (p < 0.003 and p < 0.03 compared to placebo, respectively), whereas prednisolone alone induced no significant changes. IGFBP-3 measured by WLB did not change significantly, neither did IGFBP-3 proteolysis.


CONCLUSIONS
Prednisolone administration induces only minimal changes in circulating components of the IGF axis and is not accompanied by alterations in IGFBP-3 proteolysis. This indicates that the metabolic effects of glucocorticoids do not depend on serum IGF-I.
Dall
R
R
Medical Department M, Aarhus Kommunehospital, Aarhus University, Aarhus C, Denmark. rd@dadlnet.dk
Wolthers
T
T
Flyvbjerg
A
A
Grøfte
T
T
Sandahl Christiansen
J
J
Jørgensen
J O
JO
D000328:Adult; D015153:Blotting, Western; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004347:Drug Interactions; D019382:Human Growth Hormone / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D007118:Immunoassay; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000097:blood; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000097:blood; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood*; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D007335:Insulin-Like Growth Factor II / Q000032:analysis; D008297:Male; D010919:Placebos; D011239:Prednisolone / Q000008:administration & dosage / Q000494:pharmacology*
D018970:Insulin-Like Growth Factor Binding Protein 1; D018971:Insulin-Like Growth Factor Binding Protein 2; D018972:Insulin-Like Growth Factor Binding Protein 3; D010919:Placebos; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D011239:Prednisolone