Glucocorticoid (GC) signalling is essential for normal fetal lung development. During late gestation a surge of endogenous GCs rapidly matures the lung by thinning the mesenchymal tissue and driving an increase in gas exchange surface area. Currently in situations of imminent preterm birth potent synthetic GCs such as betamethasone or dexamethasone (Dex) are administered antenatally to accelerate fetal lung maturation and reduce the risk of respiratory distress syndrome. There are however growing concerns that systemic exposure to powerful synthetic glucocorticoids is associated with detrimental side effects, particularly in the developing fetal brain. We are currently assessing novel activatable and partial agonists of the glucocorticoid receptor (GR) as new potential antenatal steroid treatments of preterm birth. One such GR agonist is a steroid prodrug called ciclesonide (Cic) that is activated in vivo by a family of serine-esterase enzymes, called the carboxylesterases (Ces). In this study we have assessed the expression of Ces enzymes in fetal organs and also compared the effect of activated Cic to dexamethasone for the regulation of key GR-regulated respiratory genes. We show that one isoform Ces1d is highly expressed in the fetal mouse lung but is absent in the brain thereby reducing Cic activation in the mouse fetal brain. To assess Cic activity in the fetal lung, primary fetal mouse fibroblast cell cultures from WT and GR-null mice were treated with Dex, Cic and its active form des-Cic for 6 hours and changes in the fibroblast transcriptome assessed by RT-qPCR. Analysis of four known GR regulated genes, Fkbp5, Crispld2, Tgm2 and Zbtb16, showed that activated Cic strongly induced expression of these genes that was dependent on a functional GR. This preliminary data indicates that Cic regulates respiratory genes in a similar way to Dex but may have negligible activation in the fetal brain thereby sparing systemic side-effects.