Developmental changes of fetal rat lung Na-K-ATPase after maternal treatment with dexamethasone

Late in gestation, the prenatal fetal alveolar epithelium switches from fluid secretion to resorption of salt and water via apical sodium channels and basal Na-K-ATPase. The amounts of lung sodium pump activity protein and mRNA increase in the lung just before birth. Because maternal glucocorticoids (GC) may promote maturation of the alveolar epithelium and augment fetal surfactant apoprotein levels, we hypothesized that GC increase the fetal lung Na-K-ATPase α- and β-subunit gene expression in development. Timed-pregnant Sprague-Dawley rats were injected daily with intraperitoneal dexamethasone (1 mg/kg) or saline for 1, 3, or 5 days before death at fetal day (FD) 17 or 19. Maternal GC treatment altered the fetal lung wet to dry weight, decreasing it at FD17 and increasing it at FD19. Northern analysis of total lung RNA for the (α₁- and β₁-pump subunits demonstrated differential regulation of the mRNA in response to GC. At FD17, β₁-mRNA increased after 1 (FD16) or 3 days (FD14-FD16) of GC treatment, whereas α₁-mRNA was not altered. There were accompanying increases in β₁-, but not α₁-, protein. At FD19, GC treatment for 5 days (FD14-FD18 increased β₁- and decreased α₁-mRNA levels, but treatment for 1 (FD18) or 3 days (FD16-FD18) had no effect. In all groups, the α₁-Na-K-ATPase protein was predominantly on the basolateral surface of airspace epithelium by immunofluorescence. In summary, maternal dexamethasone differentially affected the fetal lung mRNA levels of the two sodium pump subunits in a complex manner, with increased β₁-mRNA levels dependent on duration of treatment and fetal age.