There is evidence indicating that glucocorticoids, thyroid hormone, insulin, estrogens and catecholamines may be involved in the regulation of fetal lung maturation. The understanding of their precise role in lung growth, cell differentiation and surfactant synthesis and secretion and of the factors which modify cell sensitivity to each of these hormones is the major objective of these studies. Systems utilizing enriched populations of type II cell in suspension or in monolayer culture, lung explants in organ culture, or in vivo animal models will be used to define the role of each hormone in cell growth and differentiation (appearance of lamellar bodies), phospholipid synthesis and secretion, protein metabolism, and the synthesis and activity of enzymes involved in leuthin biosynthesis. The synergistic and antagonistic effects of hormones in these processes will be studied and the possible mechanisms involved will be investigated by measuring receptor levels and their hormonal regulation. Binding of agonists in the absence or presence of antagonists and biological response will be correlated to assert the physiological significance of the binding proteins. Since the effect of glucocorticoids, and possibly of other hormones, on lung maturation are age-dependent, some of the factors determining hormone cell responsiveness will be investigated by examining the ontogenic development of receptors, and by comparing the properties of glucocorticoid receptors and their nuclear acceptor sites, the patterns of chromosomal proteins and the effects of glucocorticoids on the synthesis or modification (acetylation, phosphorylation) of histones and nonhistones, in lungs from early and late gestation featuses and adult rabbits.