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Study of the regulation of IGF system during acute hypoxia

Abstract

The IGF system plays an important role in growth and development. IGF-I and IGF-II, are produced in the majority of the tissues and have endocrine, paracrine and autocrine actions. IGF-I and IGF-II stimulate the cellular proliferation increasing the DNA syntheses and induce the cellular differentiation mainly via their interaction with the IGF type 1 receptor (IGF1R). The IGFs are transported by six IGF-binding proteins (IGFBPs) that can control IGFs actions by regulating tissue IGFs concentrations and their interaction with IGF1R. Insulin is the main regulator of IGFBP-1 that frequently inhibits IGFs actions. GH, cortisol and glucagon collaborate in this regulation. ALS and IGFBP-3 like IGF-I are regulated by GH. The association ALS-IGFBP-3-IGF transports about 85% of the serum IGFs and constitutes the so-called ternary complex that increases the IGFs half life acting as a circulating reservoir. IGF-I and -II are important regulators of fetal growth in mice and human beings. Experimental in vivo and in vitro models of hypoxia to study the role of IGFs in intra-uterine growth retardation (IUGR) have shown several abnormalities in the IGF system. However data in humans are scarce. This prompted us to study the IGF system during acute hypoxia and try to establish the relationship between its components and blood oxygenation in children. Fifty children under 5 years of age with acute hypoxia due to acute respiratory distress will be evaluated. Blood samples for IGF-I, IGF-II, IGFBP-1, others IGFBPs, ALS, insulin and cortisol concentrations will be collected before or until 20 minutes after the oxygen therapy. IGF1R-mRNA will be obtained from the same samples for analysis. The same parameters will be analyzed at the end of oxygen therapy. Insulin and cortisol will be quantified by RIA; IGFBP-1, IGF-I,IGF-II, IGFBP-3 and ALS by ELISA. The others IGFBPs will be analyzed by Western-ligand blotting. The mRNA of IGF1R will be obtained from mononuclear cells, converted to cDNA (RT-PCR) and quantitated by real-time RT-PCR. The comparison of the data collected during and after the hypoxia, it will be possible to verify the role of blood oxygenation in the regulation of IGF system, with a particular interest in IGFBP-1 and IGF1R. (AU)

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