Abstract
Children with chronic renal failure (CRF) are often growth retarded 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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1654-1661 |
| Number of pages | 8 |
| Journal | Journal of Clinical Endocrinology and Metabolism |
| Volume | 83 |
| Issue number | 5 |
| DOIs | |
| State | Published - 1998 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Biochemistry
- Endocrinology, Diabetes and Metabolism
Cite this
The insulin-like growth factor axis and growth in children with chronic renal failure : A report of the southwest pediatric nephrology study group. / Powell, David R.; Durham, Susan K.; Liu, Frances; Baker, Bonita K.; Lee, Phillip; Watkins, Sandra L.; Campbell, Phil G.; Brewer, Eileen D.; Hintz, Raymond L.; Hogg, Ronald J.
In: Journal of Clinical Endocrinology and Metabolism, Vol. 83, No. 5, 1998, p. 1654-1661.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The insulin-like growth factor axis and growth in children with chronic renal failure
T2 - A report of the southwest pediatric nephrology study group
AU - Powell, David R.
AU - Durham, Susan K.
AU - Liu, Frances
AU - Baker, Bonita K.
AU - Lee, Phillip
AU - Watkins, Sandra L.
AU - Campbell, Phil G.
AU - Brewer, Eileen D.
AU - Hintz, Raymond L.
AU - Hogg, Ronald J.
PY - 1998
Y1 - 1998
N2 - Children with chronic renal failure (CRF) are often growth retarded 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.
AB - Children with chronic renal failure (CRF) are often growth retarded 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.
UR - http://www.scopus.com/inward/record.url?scp=7844235112&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=7844235112&partnerID=8YFLogxK
U2 - 10.1210/jc.83.5.1654
DO - 10.1210/jc.83.5.1654
M3 - Article
C2 - 9589673
AN - SCOPUS:7844235112
VL - 83
SP - 1654
EP - 1661
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
SN - 0021-972X
IS - 5
ER -