Glucocorticoids enhance fetal mammalian lung maturation as signaled by increased production of surfactant by the Type II pneumocytes. Our laboratory has reported that glucocorticoid effect on surfactant production is indirect. Glucocorticoids stimulate fetal lung fibroblasts to synthesize a fibroblast pneumocyte factor (FPF) which in turn stimulates surfactant production by the Type II alveolar epithelial cells. Since lung immaturity (respiratory distress syndrome - RDS) remains a major public health problem, further understanding of this system is necessary. Therefore, I propose to elucidate the mode of action of glucocorticoids on FPF synthesis at the protein and RNA level and determine whether glucocorticoid affects the production of FPF at a pretranslational or a posttranslational level. Subsequently, the role of other hormones on the regulation of FPF synthesis will also be examined at the protein and RNA level. Androgens for example would be of a particular interest in order to understand the differences in FPF synthesis and secretion between males and females. Finally other regulatory hormones that affect the synthesis of FPF will be further examined for their role on FPF production during different development stages. Any significant observations will be further substantiated by in vivo experiments.
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| Floros, J; Nielsen, H C; Torday, J S (1987) Dihydrotestosterone blocks fetal lung fibroblast-pneumonocyte factor at a pretranslational level. J Biol Chem 262:13592-8 |
