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

Abstract

Objectives Extremely 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. Design Newborn rats were exposed to 2, 4, 6, 8, 10, or 12 hypoxic episodes (12% O2) during hyperoxia (50% O2) from P0-P7, P0-P14 (IH), or allowed to recover from P7-P21 or P14-P21 (IHR) in room air (RA). RA littermates at P7, P14, and P21 served as RA controls; and groups exposed to hyperoxia only (50% O2) served as zero IH controls. Histopathology of the liver; hepatic levels of GH, GHBP, IGF-I, IGFBP-3, and leptin; and immunoreactivities of GH, GHR, IGF-I and IGF-IR were determined. Results Pathological findings of the liver, including cellular swelling, steatosis, necrosis and focal sinusoid congestion were seen in IH, and was 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. Conclusions IH 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.

Post-natal Growth Retardation Associated With Impaired Gut Hormone Profiles, Immune and Antioxidant Function in Pigs

“…In addition, many studies have demonstrated that IGF-1 played important roles during organ development in different animals. For example, the IGF-1 system is associated with neonatal growth in mice (38), liver development in rats (39), mammary maturation in swine (40), and bone remodeling in chickens (41). IGF-1 and GLP-1 also control the gastrointestinal tract development, inhibit the apoptosis of mammalian cells, and enhance anti-inflammatory and antioxidant capabilities (17, 36, 42).…”

Postnatal intermittent hypoxia enhances phrenic and reduces vagal upper airway motor activities in rats by epigenetic mechanisms

“…It was reported that pCIH causes hyperglycaemia and hyperinsulinaemia, and increases the levels of adrenocorticotropic hormone and corticosterone in P14 rats (Chintamaneni, Bruder, & Raff, ). Also, pCIH may disrupt growth hormone signalling, especially in the liver, impairing body and organ growth (Cai et al., ). These effects of pCIH on metabolic pathways may have contributed to the observed lower body weight gain of juvenile rats.…”

Sudden vs Pressure Wean From Nasal Continuous Positive Airway Pressure in Infants Born Before 32 Weeks of Gestation

“…18,28,[32][33][34][35] Inappropriate weaning from nCPAP may cause atelectasis, increased work of breathing, and episodes of desaturation and bradycardia, and animal studies have shown intermittent hypoxic episodes to suppress growth hormone and decrease postnatal weight gain. [36][37][38] A decreased weight gain velocity was therefore considered a biologically meaningful measure of inappropriate nCPAP weaning.…”