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 expression; and d) lung IGF- I type 1 receptor gene expression and IGF-I receptor 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. Setting: University research laboratory. Subjects: Eleven newborn rat litters (n = 10 per litter) comprised the hypoxia-exposed group and 11 litters comprised the control group (room air). Interventions: Hypoxia-group rats were placed in a chamber with an FIO₂ of 0.12 on postnatal day 1. Control group rats breathed room air. Exposure to hypoxia continued for 7 days. Measurements and Main Results: Hepatic, lung, and cardiac IGF-I mRNA levels and lung IGF-I type 1 receptor mRNA were analyzed, using the ribonuclease protection assay. Crude membrane extracts were used for competitive binding studies with IGF-I and insulin. Somatic growth in the hypoxic group was reduced by 22% (final weight: hypoxic, 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, IGF-I mRNA concentrations were significantly increased both in the heart 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 specific or nonspecific binding of IGF-I or insulin in the lung tissue. However, specific binding was 33% greater in the IGF-I compared with the insulin experiments. Conclusions: a) Hypoxia increased IGF-I mRNA in the heart, and increased both IGF-I mRNA and IGF-I type 1 receptor mRNA in the lung. b) The effects of hypoxia on IGF-I are tissue-specific.