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 alpha- and beta-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 alpha1- and beta1-pump subunits demonstrated differential regulation of the mRNA in response to GC. At FD17, beta1-mRNA increased after 1 (FD16) or 3 days (FD14-FD16) of GC treatment, whereas alpha1-mRNA was not altered. There were accompanying increases in beta1-, but not alpha1-, protein. At FD19, GC treatment for 5 days (FD14-FD18) increased beta1- and decreased alpha1-mRNA levels, but treatment for 1 (FD18) or 3 days (FD16-FD18) had no effect. In all groups, the alpha1-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 beta1-mRNA levels dependent on duration of treatment and fetal age.
Ingbar
D H
DH
Department of Medicine, University of Minnesota, Minneapolis 55455, USA.
Duvick
S
S
Savick
S K
SK
Schellhase
D E
DE
Detterding
R
R
Jamieson
J D
JD
Shannon
J M
JM
D000818:Animals; D015153:Blotting, Western; D003907:Dexamethasone / Q000494:pharmacology*; D005314:Embryonic and Fetal Development; D005260:Female; D005333:Fetus / Q000033:anatomy & histology / Q000378:metabolism* / Q000502:physiology*; D015870:Gene Expression / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology*; D007150:Immunohistochemistry; D008168:Lung / Q000201:enzymology*; D008431:Maternal-Fetal Exchange; D009929:Organ Size; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics / Q000378:metabolism*
D005938:Glucocorticoids; D003907:Dexamethasone; D000254:Sodium-Potassium-Exchanging ATPase