DEVELOPMENTAL-CHANGES OF FETAL-RAT LUNG NA-K-ATPASE AFTER MATERNAL TREATMENT WITH DEXAMETHASONE

Late in gestation, the prenatal fetal alveolar epithelium switches fro m fluid secretion to resorption of salt and water via apical sodium ch annels and basal Na-K-ATPase. The amounts of lung sodium pump activity protein and mRNA increase in the lung just before birth. Because mate rnal glucocorticoids (GC) may promote maturation of the alveolar epith elium and augment fetal surfactant apoprotein levels, we hypothesized that GC increase the fetal lung Na-K-ATPase alpha- and beta-subunit ge ne 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 a t FD17 and increasing it at FD19. Northern analysis of total lung RNA for the alpha(1)- and beta(1)-pump subunits demonstrated differential regulation of the mRNA in response to GC. At FD17, beta(1)-mRNA increa sed after 1 (FD16) or 3 days (FD14-FD16) of GC treatment, whereas alph a(1)-mRNA was not altered. There were accompanying increases in beta(1 )-, but not alpha(1)-, protein. At FD19, GC treatment for 5 days (FD14 -FD18) increased beta(1)- and decreased alpha(1)-mRNA levels, but trea tment for 1 (FD18) or 3 days (FD16-FD18) had no effect. In all groups, the alpha(1)-Na-K-ATPase protein was predominantly on the basolateral surface of airspace epithelium by immunofluorescence. In summary, mat ernal dexamethasone differentially affected the fetal lung mRNA levels of the two sodium pump subunits in a complex manner, with increased b eta(1)-mRNA levels dependent on duration of treatment and fetal age.