Preterm babies are born with a high risk of respiratory distress syndrome (RDS), as their lungs are often too immature to efficiently respire without the assistance of mechanical ventilation. This is partly due to preterm babies being born before the prepaturient fetal glucocorticoid surge, which matures the lung in preparation for birth. Currently, the only treatment for lung immaturity in preterm babies is maternal administration of synthetic glucocorticoids. However there are some adverse side effects associated with synthetic glucocorticoid use, such as a decrease in overall fetal growth and delayed brain development, which are not observed with endogenous glucocorticoids. Despite their routine use, the genomic mechanisms surrounding glucocorticoid-mediated lung development remain poorly characterised. We propose that synthetic and endogenous glucocorticoids differentially regulate specific, but different, subsets of genes leading to rapid lung maturation in the preterm, but also the inadvertent modulation of off-target genes that are possibly linked to various adverse side effects. To identify these specific gene sets, fetal rat lung fibroblast cells, isolated from Sprague Dawley rats at E20 (term ~E22), were treated for a period of 6 hours with either synthetic (Betametasone or Dexamethasone 10-6M), endogenous glucocorticoids (Corticosterone 10-6M) or vehicle as a control (0.01%). Using Next Generation RNA-sequencing (RNA-seq) we found that the overall gene expression profile is similar for both endogenous and synthetic glucocorticoids. However synthetic glucocorticoids modulated most of these genes to a higher degree compared to endogenous glucocorticoids. Quantitative PCR of novel lung specific genes modulated by glucocorticoids include Nephroblastoma overexpressed (NOV) and Transglutaminase 2 (Tgm2) showed a significantly higher expression (p<0.05) in lung fibroblast cells treated with betamethasone or corticosterone compared to fibroblasts treated with vehicle. By gaining a better understanding of the mechanisms driving glucocorticoid mediated lung development it will be possible to development better lung-specific treatments for preterm