Intermittent hypoxia suppression of growth hormone and insulin-like growth factor-I in the neonatal rat liver.

objectivesExtremely low gestational age neonates with chronic lung disease requiring oxygen therapy frequently experience fluctuations in arterial oxygen saturation or intermittent hypoxia (IH). These infants are at risk for multi-organ developmental delay, reduced growth, and short stature. The growth hormone (GH)/insulin-like growth factor-I (IGF-1) system, an important hormonal regulator of lipid and carbohydrate metabolism, promotes neonatal growth and development. We tested the hypothesis that increasing episodes of IH delay neonatal growth by influencing the GH/IGF-I axis.

designNewborn rats were exposed to 2, 4, 6, 8, 10, or 12 hypoxic episodes (12% O

resultsPathological findings of the liver, including cellular swelling, steatosis, necrosis and focal sinusoid congestion were seen in IH, and were particularly severe in the P7 animals. Hepatic GH levels were significantly suppressed in the IH groups exposed to 6-12 hypoxic episodes per day and were not normalized during IHR. Deficits in the GH levels were associated with reduced body length and increase body weight during IHR suggesting increased adiposity and catchup fat. Catchup fat was also associated with elevations in GHBP, IGF-I, leptin.

conclusionsIH significantly impairs hepatic GH/IGF-1 signaling during the first few weeks of life, which is likely responsible for hepatic GH resistance, increased body fat, and hepatic steatosis. These hormonal perturbations may contribute to long-term organ and body growth impairment, and metabolic dysfunction in preterm infants experiencing frequent IH and/or apneic episodes.