| Abstract | Children with chronic renal failure (CRF) are often growth recarded despite normal serum levels of GH and insulin-like growth factors (IGFs). Recent studies suggest that excess IGF-binding proteins (IGFBPs) in the 35-kDa fractions of CRF serum contribute to CRF growth failure. This report characterizes the relationship between IGFBP-3 and IGF peptides in the serum of growth-retarded CRF children. Size-exclusion chromatography at pH 7.4 found IGFBP-3 and IGFs almost exclusively in the 150-kDa fractions of normal serum, where their molar stoichiometry was approximately 1:1. However, similar chromatography of CRF serum found a molar excess of IGFBP-3 over total IGFs in the 150-kDa fractions and large amounts of IGFs in the 35-kDa fractions. In the 150-kDa fractions of CRF serum, IGFBP-3 was present in normal amounts, but a greater than normal amount was in the form of a 29-kDa IGFBP-3 fragment. Treatment of these CRF children with recombinant human GH increased the molar excess of IGFBP-3 over total IGFs in the 150-kDa fractions, the amount of IGFBP-3 and total IGFs in the 150-kDa fractions, and the amount of IGFs, but not IGFBPs, in the 35-kDa fractions. These data suggest that in untreated CRF children, proteolysis of IGFBP-3 in the 150-kDa fractions releases IGFs to the excess IGFBPs in the 35-kDa fractions, but insufficient IGF is released to overcome the growth-inhibiting effects of these excess IGFBPs. Treatment with recombinant human GH increases levels of IGFs and IGFBP-3 in the 150-kDa fractions, and subsequent IGFBP-3 proteolysis releases sufficient IGF to overcome the growth inhibitory effects of excess IGFBPs in the 35-kDa fractions of CRF serum. |
| Authors | D R Powell, S K Durham, F Liu, B K Baker, P D Lee, S L Watkins, P G Campbell, E D Brewer, R L Hintz, R J Hogg
(Affiliation: Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030, USA. dpowell at bcm.tmc.edu)
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| Journal | The Journal of clinical endocrinology and metabolism
(J Clin Endocrinol Metab)
Vol. 83
Issue 5
Pg. 1654-61
(May 1998)
ISSN: 0021-972X UNITED STATES |
| PMID | 9589673
(Publication Type: Clinical Trial, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, U.S. Gov't, P.H.S.)
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| Chemical References |
- Insulin-Like Growth Factor Binding Protein 3
- Human Growth Hormone
- Insulin-Like Growth Factor I
- Insulin-Like Growth Factor II
|
| Topics |
- Child
- Child, Preschool
- Chromatography, Gel
- Female
- Growth
- Human Growth Hormone
(blood, therapeutic use)
- Humans
- Immunoblotting
- Insulin-Like Growth Factor Binding Protein 3
(blood)
- Insulin-Like Growth Factor I
(metabolism)
- Insulin-Like Growth Factor II
(metabolism)
- Kidney Failure, Chronic
(physiopathology)
- Male
|
