EFFECT OF HYPOXIA ON LUNG, HEART, AND LIVER INSULIN-LIKE GROWTH-FACTOR-I GENE AND RECEPTOR EXPRESSION IN THE NEWBORN RAT

Objectives: We examined the effect of 7 days of hypoxia in the newborn rat on: a) body, heart, and lung growth; b) circulating insulin like growth factor-I (IGF-I); c) lung, heart, and liver IGF-I gene expressi on; and d) lung IGF I type 1 receptor gene expression and IGF-I recept or binding, We hypothesize that hypoxic exposure would modify body and organ growth and alter IGF-I gene and receptor expression in an organ specific manner. Design: Randomized, controlled prospective study. Se tting: University research laboratory. Subjects: Eleven newborn rat li tters (n = 10 per litter) comprised the hypoxia exposed group and 11 l itters comprised the control group (room air). Interventions: Hypoxia- group rats were placed in a chamber with an F-IO2 of 0.12 on postnatal day 1. Control group rats breathed room air, Exposure to hypoxia cont inued for 7 days. Measurements and Main Results: Hepatic, lung, and ca rdiac IGF-I mRNA levels and lung IGF I type 1 receptor mRNA were analy zed, using the ribonuclease protection assay, Crude membrane extracts were used for competitive binding studies with IGF-I and insulin, Soma tic growth in the hypoxic group was reduced by 22% (final weight: hypo xic, 14.8 +/- 1.2 g; control, 17.1 +/- 1.5 g; p < .001), The relative weight (organ weight/body weight [mg/g]) of the heart was increased by 39% (p < .001) in the hypoxic pups compared with the normoxic animals , while the relative weight of the lung was unchanged, With hypoxia, I GF-I mRNA concentrations were significantly increased both in the hear t and lung (30% and 33%, respectively, p < .02); but, in contrast, IGF -I mRNA concentrations were not significantly different in the liver, The IGF-I receptor mRNA in the lung was increased by 200% (p < .02) in hypoxia compared with controls, There was no effect of hypoxia on spe cific or nonspecific binding of IGF-I or insulin in the lung tissue, H owever, specific binding was 33% greater in the IGF-I compared with th e insulin experiments. Conclusions: a) Hypoxia increased IGF-I mRNA in the heart, and increased both IGF-I mRNA and IGF I type 1 receptor mR NA in the lung. b) The effects of hypoxia on IGF-I are tissue-specific .