This is a Program Project entitled 'The Biological Basis for Perinatal Transition' which reflects our interest in the development of the mammalian fetus and its transition to postnatal life. We view the postconceptual development of the mammalian fetus as characterized by several critical themes: organogenesis, regulation of somatic growth, maturation of key endocrine axes, and preparation for postnatal life. Development emphasizes these themes by progression through a series of only partially understood, but carefully choreographed, maturational steps. Each process significantly impacts the outcome of subsequent milestones. For example, the ontogeny of the fetal hypothalamic- pituitary-adrenocortical axis has been extensively studied. In mammalian fetal development an increase in late gestation in the production of cortisol is a key hormonal trigger for maturation of many key organ systems and other hormonal axes. The role of insulin in regulating late gestation fetal liver growth and functional differentiation is another example. In contrast, placental differentiation and syncytiotrophoblast formation is largely under the influence of maternal hormonal factors. In all cases, perturbation of these mechanisms has pathophysiologic consequences for the fetus and newborn which are relevant to clinical conditions. This Program Project Grant will support research designed to define how several of these events impact fetal and newborn development. We will study as model systems: the factors which regulate proliferation and differentiation of developing the trophoblast factors which regulate the growth and proliferation of fetal and neonatal hepatocytes; unique mechanisms for hormonal regulation of gene transcription between fetal and adult life; the role of glucocorticoids in the regulation of critical aspects of brain maturation.
