The Na+ pump, Na+-K+-ATPase, along with the Na+ channel is essential for th
e removal of alveolar solute and fluid perinatally. Because Na+-pump mRNA a
nd activity increase before birth and maternal glucocorticoids (GCs) influe
nce Na+-K+-ATPase mRNA expression in fetal rat lung, we hypothesized that G
Cs increased Na+-K+-ATPase gene expression in a fetal lung epithelial cell
line. After 24 h of exposure, dexamethasone increased the steady-state leve
ls of Na+-K+-ATPase alpha(1) and beta(1) mRNA in a fetal rat lung epithelia
l cell line in a dose-dependent fashion (10(-7) to 10(-5) M). The maximal i
ncrease in mRNA levels was 3.8-fold for al and 2.8-fold for beta(1). The in
crease in mRNA was detected as early as 6 h for the beta(1)-subunit and 18
h for the alpha(1)-subunit, and both peaked at 24 h. This gene upregulation
was not due to increased mRNA stability based on mRNA half-life determinat
ion after actinomycin D inhibition. Transfection experiments with alpha(1)
and beta(1) promoter-reporter constructs demonstrated 3.2 +/- 0.5- and 2.6
+/- 0.4-fold increases, respectively, in promoter activity, consistent with
transcriptional activation of the promoter-reporter construct. These findi
ngs, increased promoter activity with no change in stability, indicate that
GCs increased Na+-K+-ATPase transcription in a fetal lung epithelial cell
line.