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http://purl.uniprot.org/citations/24926947http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/24926947http://www.w3.org/2000/01/rdf-schema#comment"

Background

IGF-I is mainly sequestered in a 150-kDa ternary complex with IGF binding protein (IGFBP)-3 and the acid-labile subunit. Data on complex formation and factors influencing formation have not been established. Dissociation of IGF-I from the ternary complex is in part regulated by proteolysis of IGFBP-3, which reduces its affinity for IGF-I. Short small for gestational age (SGA) children have lower IGF-I and IGFBP-3 levels compared with healthy peers.

Objective

The objective of the study was to determine complex formation in healthy normal-statured children and assess variables influencing complex formation. Second, we determined complex formation in short SGA children.

Design/methods

Complex formation was assessed using (125)I-hIGF-I column chromatography in 70 controls (40 boys), median age 10.6 years, and 40 short SGA children (25 boys), median age 8.6 years. IGFBP-3 was determined by Western immunoblotting.

Results

(125)I-hIGF-I complex formation showed an age-specific pattern in healthy controls. Variables positively influencing ternary complex formation were higher serum IGF-I levels compared with IGFBP-3 levels (P < .001) and lower serum IGF-II (P < .001) and IGFBP-1 levels (P < .001). In addition, a higher presence of proteolyzed IGFBP-3 negatively influenced 150-kDa complex formation (P = .006). At a young age, healthy children showed considerable IGFBP-3 proteolytic activity, which declined with aging (P < .001). IGFBP-3 proteolytic activity was negatively correlated with IGF-I levels (P < .001). Compared with healthy controls, short SGA children showed reduced IGF-I levels (-1.3 vs 0.1 SD score) and increased proteolyzed IGFBP-3 (35.1% vs 12.2%).

Conclusion

Age-specific normative values for (125)I-hIGF-I 150-kDa ternary complex formation are presented. A decrease in IGF-I and an increase in IGF-II, IGFBP-1, and IGFBP-3 proteolytic activity associate with reduced (125)I-hIGF-I ternary complex formation. Our results suggest that in conditions in which IGF-I levels are low, such as young age and in short SGA children, IGFBP-3 proteolytic activity is increased to ensure IGF-I bioavailability."xsd:string
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http://purl.uniprot.org/citations/24926947http://purl.uniprot.org/core/author"Hokken-Koelega A.C."xsd:string
http://purl.uniprot.org/citations/24926947http://purl.uniprot.org/core/author"van Doorn J."xsd:string
http://purl.uniprot.org/citations/24926947http://purl.uniprot.org/core/author"Renes J.S."xsd:string
http://purl.uniprot.org/citations/24926947http://purl.uniprot.org/core/date"2014"xsd:gYear
http://purl.uniprot.org/citations/24926947http://purl.uniprot.org/core/name"J Clin Endocrinol Metab"xsd:string
http://purl.uniprot.org/citations/24926947http://purl.uniprot.org/core/pages"E1988-96"xsd:string
http://purl.uniprot.org/citations/24926947http://purl.uniprot.org/core/title"Ternary complex formation and IGFBP-3 proteolytic activity during childhood: age-dependent changes."xsd:string
http://purl.uniprot.org/citations/24926947http://purl.uniprot.org/core/volume"99"xsd:string
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