Developmental changes of fetal rat lung na,k-atpase following
maternal treatment with dexamethasone.
Ingbar, David H., Sara Duvick, S. Kay Savick, Dennis E. Schellhase,
Robin Detterding, James D. Jamieson, and John M. Shannon.
Department of Medicine, University of Minnesota, Minneapolis, MN;
Departments of Medicine and Cell Biology, Yale University School of
Medicine, New Haven, CT, and Departments of Medicine and Pediatrics,
National Jewish Asthma Center and the University of Colorado Health
Sciences Center, Denver, CO
APStracts 3:0205L, 1996.
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. Since 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 i.p.
dexamethasone (1 mg/kg) or saline for 1, 3, or 5 days prior to
sacrifice 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
[alpha]-1 and [beta]-1 pump subunits demonstrated differential
regulation of the mRNA in response to GC. At FD17, [beta]-1 mRNA
increased after one (FD16) or three days (FD14-16) of GC treatment,
while [alpha]-1 mRNA was not altered. There were accompanying
increases in [beta]-1, but not [alpha]-1, protein. At FD19, GC
treatment for five days (FD14-18) increased [beta]-1 and decreased
[alpha]-1 mRNA levels, but treatment for 1 (FD18) or 3 days (FD16-18)
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, maternal dexamethasone differentially
affected the fetal lung mRNA levels of the two sodium pump subunits
in a complex manner, with increased [beta]-1 mRNA levels dependent
upon duration of treatment and fetal age.
Received 4 October 1994; accepted in final form 11 November 1996.
APS Manuscript Number L291-4.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 31 December 1996