Abstract 572 Neonatal Disease Oriented Research: Steroids & Oxygen: Perinatal Effects Poster Symposium, Sunday, 5/2

Glucocorticoids (GC) are used in neonatal intensive care units to prevent bronchopulmonary dysplasia, however the long term consequences remain undefined. To determine the adult effects of neonatal GC therapy, we administered 0.2 mg/kg of dexamethasone (Dx; n=11 litters) or vehicle (V; n=12 litters) intraperitoneally from 2d to 7d daily, and the body weight gain, food and water intake were assessed after weaning (22d) at 35d, 60d, and 120d in males ("n"-Dx=3, V=9 at each age) and females ("n"-Dx=8, V=3). The data were analyzed by the Wilcoxan-Mann Whitney test using exact significance levels. Body weight gain (g) was 25-35% lower at 35d, 60d, & 120d in the Dx vs V in both males (p=0.009) and females (p=0.02). Food intake (g/d) declined only in the 35d (p=0.005) and 60d (0.027) males with no change in water intake (ml/d) in both males and females. To delineate the mechanism(s) for these phenotypic changes, floating microtome brain (hypothalamic) sections were examined. Dx treatment caused a 50% increase in the paraventricular neuropeptide Y (NPY; orexigenic) immunoreactivity only in the 120d females (p=0.02) with no change in the males. On the other hand, Dx had no effect on the adult hypothalamic α-melanocyte-stimulating hormone (MSH; anorexigenic) or the leptin receptor immunoreactivity in both females and males. While no changes were observed in plasma glucose, insulin, corticosterone, and leptin concentrations in the female at all three ages, a decline in plasma glucose (p=0.009), insulin (p=0.024), and leptin (p<0.05) levels with a normal corticosterone level was observed only in the 120d males. We conclude that postnatal systemic GC treatment caused: 1] a decline in the adult body weight gain pattern in both males and females, 2] an increase in hypothalamic NPY only in adult females with no change in either the leptin receptors or the MSH levels, 3] a decrease in food intake only in adult males with no change in water intake, and 4] a decrease in circulating levels of glucose, insulin and leptin in adult males. We speculate that the neonatal GC induced hypothalamic NPY synthesis/release in the adult females normalized the food intake and hormonal milieu. In contrast, in the adult males, the lack of an increase in hypothalamic NPY led to a continued decline in food intake resulting in a catabolic hormonal milieu.

Supported by [NIH-HD-25024 & HD-33997].