Am J Physiol Cell Physiol AJP: Endocrinology and Metabolism
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Am J Physiol Cell Physiol (June 5, 2002). doi:10.1152/ajpcell.00029.2002
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Articles in PresS, published online ahead of print June 5, 2002
Am J Physiol Cell Physiol, 10.1152/ajpcell.00029.2002
Submitted on January 20, 2002
Accepted on April 29, 2002

Endogenous and Exogenous Glucocorticoid Regulation of ENaC mRNA Expression in Developing Kidney and Lung

Kenzo Nakamura1, John B. Stokes1, and Paul B. McCray, Jr.2*

1 Internal Medicine, University of Iowa College of Medicine and VA Medical Center, Iowa City, IA, USA
2 Pediatrics, University of Iowa College of Medicine, Iowa City, IA, USA

* To whom correspondence should be addressed. E-mail: paul-mccray{at}uiowa.edu.

Lung liquid absorption at the time of birth is crucial for the successful onset of respiration. Na absorption by the renal collecting duct plays an important role in renal fluid and electrolyte homeostasis during the early postnatal period. The epithelial Na channel (ENaC) plays a central role in mediating these functions and its subunit expression is developmentally regulated in a temporal and tissue specific pattern. Several lines of evidence suggest that the prenatal increase in circulating glucocorticoids may play an important role in increasing ENaC expression during maturation. We tested the role of the prenatal surge using CRH (corticotropin releasing hormone) knock-out (KO) mice. Relative ENaC expression in the lungs of the KO mice increased at the same rate as the wild type mice, but the absolute expression was only 20-30% of the wild type. In contrast, relative and absolute expression of all three subunits in the kidneys was not different between KO and wild type mice. Dexamethasone, a non-metabolized glucocorticoid, increased {alpha}-ENaC mRNA in fetal lung and kidney explants within 24 h, but had different effects on ß- or {gamma}-ENaC. Dexamethasone increased ß- and {gamma}-ENaC in lung, but only after more than 48 h of exposure and had no effect on kidney. These results suggest that the kidney metabolizes endogenous glucocorticoids, while the lung does not. Furthermore, the marked difference between lung and kidney responsiveness to glucocorticoids in ß- and {gamma}-ENaC expression suggests that factors other than steroids may be important in regulating functional ENaC expression during development.




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