Unbound/Bioavailable IGF-I Enhances

HÉCTOR G. JASPER; HORACIO M. DOMENÉ; LILIANA M. KARABATAS; CLARA GUIDA; SHOSHANA YAKAR

Cartagena de Indias

Congreso; XXII Annual Meeting of the Sociedad Latinoamericana de Endocrinología Pediátrica (SLEP); 2011

Sociedad Latinoamericana de Endocrinología Pediátrica (SLEP)

Unbound/Bioavailable IGF-I Enhances Somatic Growth H. Jasper1, H. Domené1, L. Karabatas1, C. Guida1, S. Yakar2 ¹Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET) y Hospital de Niños R. Gutiérrez;División de Endocrinologia; ²Mount Sinai School of Medicine Division de Endocrinology -Diabetes and Bone Disease, NY, USA Introduction and Objectives: Des1-3-IGF-I (DES) is an IGF-I analog with normal affinity for the IGF-I receptor but reduced affinity to IGFBPs. To determine whether IGF-I binding to IGFBPs is necessary for normal growth, we generated a knock-in mouse model of DES-IGF-I (KID). Methods: In KID the Igf1 gene was replaced by des-Igf1, and therefore expressed under the endogenous Igf1 promoter. Serum determinations: DES by RIA, IGF-I by RIA, IGBP-3 by ELISA, ALS by immunoblot, ternary complex formation (TCF) using either iodinated IGF-I or DES as tracers. Results: See table. Compared to controls KID increased body weight and length, relative weights of kidney, pancreas, uterus and ovaries (p < 0.05). Serum DES was reduced (p < 0.0001). KID TCF was reduced when WT-IGF-I was used as a tracer (p < 0.01); bound IGF cpm/total cpm was reduced in KID (p < 0.001) when DES IGF-I was used as tracer. Conclusion: Despite reductions in serum IGF and TCF, KID exhibited increased body weight and length, but not all organs responded equally. DES lower affinity for IGFBPs, reducing bound-IGFs in KID, suggests that an increase in bioactive DES (free plus that loosely bound to IGFBPs) at the target organ is responsible for KID´s increased body size and selective organ.