Ternary complex formation and IGFBP-3 proteolytic activity during childhood: age-dependent changes

Area of Science:

• Endocrinology
• Pediatric Growth

Background:

• Insulin-like Growth Factor I (IGF-I) is primarily bound in a 150-kDa complex with IGF binding protein (IGFBP)-3 and the acid-labile subunit.
• IGFBP-3 proteolysis reduces IGF-I affinity, impacting IGF-I bioavailability.
• Short small for gestational age (SGA) children exhibit lower IGF-I and IGFBP-3 levels compared to healthy peers.

Purpose of the Study:

• To determine IGF-I ternary complex formation in healthy children and identify influencing factors.
• To assess IGF-I ternary complex formation in short SGA children.

Main Methods:

• Utilized (125)I-hIGF-I column chromatography to assess complex formation in 70 healthy controls and 40 short SGA children.
• Quantified IGFBP-3 levels using Western immunoblotting.

Main Results:

• Observed an age-specific pattern in IGF-I ternary complex formation in healthy controls.
• Higher serum IGF-I/IGFBP-3 ratios, lower IGF-II, and lower IGFBP-1 levels positively influenced complex formation.
• Increased IGFBP-3 proteolysis negatively impacted 150-kDa complex formation, particularly in younger children and SGA individuals.

Conclusions:

• Established age-specific normative values for (125)I-hIGF-I 150-kDa ternary complex formation.
• Decreased IGF-I and increased IGF-II, IGFBP-1, and IGFBP-3 proteolytic activity are associated with reduced IGF-I ternary complex formation.
• Elevated IGFBP-3 proteolytic activity in conditions of low IGF-I, such as in young children and SGA individuals, appears to enhance IGF-I bioavailability.