Abstract 1672 Neonatal Disease Oriented Research: Steroids & Oxygen: Perinatal Effects Poster Symposium, Sunday, 5/2

The postnatal use of glucocorticoids (GC) to ameliorate bronchopulmonary dysplasia has raised concerns regarding the catabolic side effects. To determine the mechanisms responsible for GC induced body weight loss, 2-7d old rats received mg/kg of dexamethasone (Dx; n=11 litters) or Vehicle (V; n=12 litters) intraperitoneally on a daily basis, and the effect upon the body wt. gain pattern, food and water intake, appetite regulating hypothalamic neuropeptides, and the peripheral hormonal milieu was examined during the suckling phase. Data were analyzed by the Wilcoxan-Mann Whitney test using exact significance levels. Dx led to a persistent decline in body weight throughout the suckling phase (3d [99%] to 22d [50%]; p=0.0001). This decline in body weight was associated with a 50% decline in food (g/d; p=0.005) and a 40% decline in water intake (ml/d; p=0.01) upon weaning at 22d in both males and females. Examination of brain (hypothalamic) floating microtome sections revealed a 20-50% increase in the paraventricular neuropeptide Y (NPY; orexigenic) immunoreactivity at 8d and 22d in the Dx vs V (p=0.02), with no change in the α-melanocyte stimulating hormone (MSH; anorexigenic) or the leptin receptor immunoreactivity. Peripherally, an initial 55% decline in circulating corticosterone concentrations was noted at 3d (p=0.01) which later normalized between 8d-22d. In contrast, an initial 1.5-fold increase in plasma leptin levels was observed at 3d (p=0.0095) followed by a 75-90% decline subsequently between 8d and 15d (p=0.016), with no change at 22d. These pertubations were associated with a 40-50% decline in plasma glucose at 8d and 15d (p=0.04) and no change in insulin concentrations throughout the suckling phase. At 8d and 22d, there was a 25% increase in skeletal muscle insulin-responsive glucose transporter (Glut 4) levels (p<0.05). We conclude that postnatal systemic Dx caused 1] a persistent loss in body weight due to a diminution in food and water intake, 2] no change in the hypothalamic anorexigenic α-MSH levels with a compensatory increase in the orexigenic NPY amounts, and 3] a persistent decline in circulating glucose and leptin concentrations with an increased insulin sensitivity (Glut 4) during the suckling phase. We speculate that the postnatal GC induced body weight loss is due to a decrease in appetite which cannot be overcome by the GC induced NPY release. The decrease in food intake results in a hormonal/metabolic mileu consistent with starvation. [Supported by NIH-HD 25024 & HD 33997].