Respiratory function at birth is a critical event in the survival of the neonate. The overall objective of this interdisciplinary project (biochemistry, endocrinology, physiology) is to investigate how altered nutrient supply (directly or indirectly) affects lung dynamics and cellular function. The specific aims of this proposed three year project is to investigate the interaction of altered nutrient supply and hormones on surfactant lipids (synthesis and remodeling) and hormone receptor function. The proposed investigation will focus on mechanisms by which the hypoglycemic/hyperglycemic state alters the regulation of surfactant lipid pathway enzymes and hormone receptor function in the perinatal lung. This will be accomplished by in vivo studies and by in vitro studies using fetal lung organ explant culture. Pregnant rats will either be fasted, infused with insulin, fed a high sucrose diet, or infused with glucose and the prematurely delivered pups analyzed for blood substrate (glucose, lactate, fatty acids, and glycerol) and hormone (insulin, glucagon, glucocorticoid, thyroxine, and prolactin) levels. Rates of fatty acid synthesis and phosphatidylcholine synthesis and remodeling to surfactant will also be determined along with activities of key regulatory enzymes. The direct effect of changes in these substrates and hormones on the lung will be determined in the culture system. These well controlled in vivo and in vitro studies will provide critical information about altered nutrient supply and effects on cellular function of the perinatal lung.