Insulin-like growth factor I and its binding proteins in the experimental nephrotic syndrome.
Insulin-like growth factor I (IGF-I) is present in serum in association with specific IGF-binding proteins (IGFBPs) primarily in a large (approximately 150K) ternary or a smaller (approximately 50K) binary protein complex or in the free form (< or = 1%). We hypothesized that glomerular proteinuria results in urinary excretion of IGF-I/IGF-binding protein complexes and that the nephrotic syndrome induces abnormal serum distribution and liver synthesis of IGF-binding proteins. In nephrotic rats, serum IGF-I levels are reduced compared with pair-fed control animals. In nephrotic rat serum, binding to IGFBP-3 is reduced and Western immune analysis demonstrates an approximately 27K fragment that does not bind IGF-I, suggesting in vivo proteolysis of IGFBP-3. In contrast, binding and serum levels of IGFBP-2 are increased in nephrotic rats, which results from increased synthesis in the liver. In Nagase analbuminemic rats, the IGF-I levels and IGFBP-distribution in serum are normal suggesting that the reduced albumin levels in the nephrotic syndrome do not cause the increased liver synthesis and serum levels of IGFBP-2. Nephrotic rat urine contains IGFBP-3 and IGFBP-2 as well as strong activity of an IGFBP-3 protease. Because the 150K ternary complex in serum but not the smaller binding protein complex is restricted to the intravascular space, the shift of binding from IGFBP-3 (ternary complex) to IGFBP-2 (binary complex) in nephrotic rat serum may help to maintain tissue availability despite the reduction in serum IGF-I levels.
Hirschberg
R
R
Division of Nephrology and Hypertension, Harbor-University of California at Los Angeles Medical Center, Torrance 90509.
Kaysen
G A
GA
D000818:Animals; D015153:Blotting, Western; D002352:Carrier Proteins / Q000378:metabolism* / Q000652:urine; D004317:Doxorubicin; D006031:Glycosylation; D015151:Immunoblotting; D018971:Insulin-Like Growth Factor Binding Protein 2; D018969:Insulin-Like Growth Factor Binding Proteins; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008297:Male; D009404:Nephrotic Syndrome / Q000139:chemically induced / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D002352:Carrier Proteins; D018971:Insulin-Like Growth Factor Binding Protein 2; D018969:Insulin-Like Growth Factor Binding Proteins; D007334:Insulin-Like Growth Factor I; D004317:Doxorubicin