Serum profiles of insulin-like growth factors and their binding proteins in adults with growth hormone receptor deficiency treated with insulin-like growth factor I.
Six adult patients with growth hormone receptor deficiency (GHRD) (2 men, 4 women) with an identical defect in the growth hormone receptor (GHR) gene, were treated with recombinant human insulin-like growth factor I (IGF-I), 40 micrograms/kg s.c. twice daily, for 7 days. Serum concentrations of IGF peptide and IGF binding protein-3 (IGFBP-3) were measured by specific radioimmunoassays; serum IGFBPs were also measured by Western ligand blotting. The size distribution of both IGF-I and IGF-II was measured in serum following size-exclusion fast-performance liquid chromatography. IGF-I treatment resulted in a normalization of serum IGF-I levels on days 1-7 of treatment and a decrease in serum IGF-II levels. The fall in IGF-II levels and the simultaneous rise in IGF-I levels, however, resulted in an unchanged total serum IGF level. The low IGFBP-3 values did not significantly change during treatment, whereas there was a slight increase in IGFBP-2 levels. Preliminary analysis of size-fractionated sera suggested an increase in IGF-I levels in the 40 and 150 kDa regions at the expense of IGF-II levels. The results suggest that despite the failure of IGF-I treatment to increase IGFBPs significantly, serum IGFBP concentrations were sufficient to maintain normal levels of IGF-I.
Fielder
P J
PJ
Department of Pediatrics, Stanford University School of Medicine, California.
Gargosky
S E
SE
Vaccarello
M
M
Wilson
K
K
Cohen
P
P
Diamond
F
F
Guevara-Aguirre
J
J
Rosenbloom
A L
AL
Rosenfeld
R G
RG
D000328:Adult; D015153:Blotting, Western; D002352:Carrier Proteins / Q000097:blood*; D002850:Chromatography, Gel; D002851:Chromatography, High Pressure Liquid; D005260:Female; D030342:Genetic Diseases, Inborn / Q000097:blood / Q000188:drug therapy* / Q000235:genetics; D006130:Growth Disorders / Q000097:blood / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D007279:Injections, Subcutaneous; D018971:Insulin-Like Growth Factor Binding Protein 2; D018969:Insulin-Like Growth Factor Binding Proteins; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage / Q000032:analysis / Q000494:pharmacology / Q000627:therapeutic use*; D007335:Insulin-Like Growth Factor II / Q000032:analysis*; D008297:Male; D008970:Molecular Weight; D010641:Phenotype; D011863:Radioimmunoassay; D011986:Receptors, Somatotropin / Q000235:genetics; D013577:Syndrome
D002352:Carrier Proteins; D018971:Insulin-Like Growth Factor Binding Protein 2; D018969:Insulin-Like Growth Factor Binding Proteins; D011986:Receptors, Somatotropin; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II