CORRELATION OF SURFACTANT PHOSPHATIDYLCHOLINE SYNTHESIS AND 11-BETA-HYDROXYSTEROID DEHYDROGENASE IN THE FETAL LUNG

Glucocorticosteroids (GCS) are prerequisite for the induction of surfa ctant synthesis in the fetal lung. The 11 beta-hydroxysteroid dehydrog enase (11 beta-HSD) regulates the intracellular concentration of biolo gically active GCS. In this study we demonstrate the correlation of 11 beta-HSD activity and the GCS-induced surfactant phosphatidylcholine synthesis in organoid cultures of fetal rat lung. In the first series of experiments, [H-3]corticosterone (CORT) or [H-3]11-dehydrocorticost erone (11-DHC) were added to lung organoid cultures to test 11 beta-HS D activity. We found a low oxidative and a high reductive conversion i ndicating that in intact cells the equilibrium tends to biologically a ctive GCS. However, in homogenized organoid cultures oxidative outweig hed reductive activity. Secondly, the phosphatidylcholine synthesis of organoid cultures was enhanced by preincubation with GCS. CORT, as we ll as the hormonally inactive 11-DHC, increased the incorporation of [ C-14]choline into phosphatidylcholine. The effect of the latter was co mpletely inhibited by glycyrrhetinic acid (inhibitor of 11 beta-HSD) i ndicating that it is caused by a previous conversion of 11-DHC into CO RT via 11 beta-HSD. Thirdly, preincubation with GCS also altered 11 be ta-HSD activity: dexamethasone or CORT both decreased the oxidative an d increased the reductive activity in intact cells, indicating that gl ucocorticoids increase the rate of their own activation by positive fe edback.