bromochloroacetic-acid and 11-dehydrocorticosterone

Glucocorticoids (GCs) induce surfactant synthesis in the late foetal lung. Deficient GC action causes respiratory distress syndrome (RDS). 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) converts inert cortisone (11-dehydrocorticosterone in rodents) into active cortisol (corticosterone), thus amplifying intracellular GC action. Reduction or loss of pulmonary 11beta-HSD1 activity in glycyrrhetinic acid-treated rats substantially impaired foetal lung maturation (Hundertmark et al., Horm Metab Res, this issue). To test these data, we investigated 11beta-HSD1 activity and lung maturity in the late foetal lung using 11beta-HSD1 knockout mice. Control foetal mice showed high 11beta-HSD activity in the late foetal lung and levels of plasma 11-dehydrocorticosterone were high. Lungs from 11beta-HSD1 -/- mice had lower surfactant protein-A (mRNA and protein) levels and significant depletion of lung surfactant according to both light and electron microscopy, and also had reduced amniotic fluid lecithin/sphingomyelin ratios. These results support the previous experiments with glycyrrhetinic acid and emphasize the importance of 11beta-HSD1 in foetal lung maturation.

Topics: 11-beta-Hydroxysteroid Dehydrogenases; Amniotic Fluid; Animals; Animals, Newborn; Corticosterone; Embryonic and Fetal Development; Female; Glycyrrhetinic Acid; Hydroxysteroid Dehydrogenases; Keratins; Lung; Mice; Mice, Knockout; Microscopy, Confocal; Microscopy, Electron; Phosphatidylcholines; Pregnancy; Pulmonary Surfactant-Associated Protein A; RNA, Messenger; Sphingomyelins