The long-term objective of the Center is to optimize fetal and neonatal growth and to decrease fetal and infant morbidity and mortality. These goals will be accomplished by defining and understanding the basic physiology of fetal and neonatal growth and growth retardation. The overall thesis examined is that specific growth factors are principal regulators of growth and development of the fetus and infant. Drs. Tsang, Clark, Handwerger, and Whitsett provide the administrative organizational framework for the PERC. The Molecular Core provides a central site for molecular norphologic studies and training in in situ hybridization and immunocytochemistry, directed by Dr. Jeff Whitsett. Drs. Korfhagen and Whitsett will identify a progenitor during branching morphogenesis and Type II cytodifferentiation in the fetal lung. Drs. Weaver and Drake will test the hypothesis that the temporal and spatial regulation of pulmonary glycogen metabolism, in the developing respiratory epithelium, is correlated with the pre-translational regulation of glycogen synthase (Project B) and phosphorylase kinase (Project A). Dr. Lieberman examines the thesis that injections of neonatal rats with epidermal growth factor alters ontogenic expression of fibroblast growth factors (FGFs). Drs. Hoath and Donnelly test the thesis that perturbations of perinatal growth; i.e. placental insufficiency or exposure to exogenous EGF, will alter molecular events of early homeothermic adaptation in brown adipose tissue and imprint aberrant patterns of metabolic function in adults. Drs. Chernausek and Smith examine the thesis that carrier proteins for insulin- like growth factors are physiologically-regulated modulators of IGF action during the perinatal period. Dr. Iwamoto tests the hypothesis that the placenta and fetal liver regulated plasma concentrations of IGF-I and thus coordinate fetal growth. Dr. Clark tests the thesis that chronic reduced uteroplacental blood flow leads to asymmetric growth retardation and reduced IGF-I by altering delivery and uptake of oxygen, glucose, and amino acids by the placenta and fetus while also testing the thesis that direct fetal supplementation with nutrients and maternal oxygen administration can prevent IUGR. Thus in this Center, molecular biologic, cellular, physiologic, and a clinical study complement each other in an integrated multidisciplinary study.