Proteolysis of insulin-like growth factor-binding protein-3 in human immunodeficiency virus-positive children who fail to thrive.

Abstract

Failure to thrive is a common manifestation of human immunodeficiency virus (HIV) infection in children. Given the role of insulin-like growth factor I (IGF-I) in stimulating postnatal growth, we have examined whether HIV-infected pediatric patients with growth failure have lower serum concentrations of IGF-I than age-matched control subjects. IGF-I was measured in 16 HIV-infected children and 13 HIV-negative controls. Ten of the HIV-infected children failed to thrive based on height and linear growth that was below the National Center for Health Statistics 10th percentile. IGF-I levels were significantly lower in children who failed to thrive compared to those in age-matched controls (20 vs. 60 micrograms/L; P < 0.001). Children who failed to thrive also displayed lower IGF-I levels than HIV-positive children, who exhibited normal growth velocity (20 vs. 91 micrograms/L; P < 0.001). Failure to thrive was associated with a significant reduction in circulating levels of IGF-binding protein-3 (IGFBP-3), as determined by ligand and Western blotting (P < 0.001), enhanced IGFBP-3 proteolysis (P < 0.001), and a decrease in the serum concentration of the acid-labile subunit of the IGFBP-3 ternary complex (P < 0.005). IGFBP-3 proteolysis was negatively correlated with IGF-I (r = 0.78) and IGFBP-3 levels (r = 0.70). Failure to thrive was associated with a reduction in the formation of the ternary complex, but the ternary complex could be restored by the addition of an excess of IGFBP-3 to serum. These results indicate that low levels of IGF-I, IGFBP-3, and acid-labile subunit are associated with a failure to thrive in HIV-infected children.

• Authors: R A Frost, S A Nachman, C H Lang, M C Gelato
• Journal: The Journal of clinical endocrinology and metabolism (J Clin Endocrinol Metab) Vol. 81 Issue 8 Pg. 2957-62 (Aug 1996) ISSN: 0021-972X [Print] United States
• PMID: 8768858 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Insulin-Like Growth Factor Binding Protein 3
• Insulin-Like Growth Factor I
• Peptide Hydrolases

Topics

• Blotting, Western
• Child
• Child, Preschool
• Electrophoresis, Polyacrylamide Gel
• Failure to Thrive (etiology)
• HIV Seropositivity (complications, metabolism)
• Humans
• Infant
• Insulin-Like Growth Factor Binding Protein 3 (chemistry, metabolism)
• Insulin-Like Growth Factor I (metabolism)
• Peptide Hydrolases (metabolism)