Endogenous and exogenous glucocorticoid regulation of ENaC mRNA expression in developing kidney and lung

Kenzo Nakamura; John B Stokes; Paul B McCray Jr

doi:10.1152/ajpcell.00029.2002

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Endogenous and exogenous glucocorticoid regulation of ENaC mRNA expression in developing kidney and lung

Journal article

Peer reviewed

Endogenous and exogenous glucocorticoid regulation of ENaC mRNA expression in developing kidney and lung

Kenzo Nakamura, John B Stokes and Paul B McCray Jr

American Journal of Physiology: Cell Physiology, Vol.283(3), pp.C762-772

09/2002

DOI: 10.1152/ajpcell.00029.2002

PMID: 12176733

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Abstract

Lung liquid absorption at 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 corticotropin-releasing hormone (CRH) knockout (KO) mice. Relative ENaC expression in lungs of KO mice increased at the same rate as in wild-type (WT) mice, but absolute expression was only 20-30% of WT. In contrast, relative and absolute expression of all three subunits in kidneys was not different between KO and WT mice. Dexamethasone (Dex) increased alpha-ENaC mRNA in fetal lung and kidney explants within 24 h but had different effects on beta- or gamma-ENaC. Dex increased beta- and gamma-ENaC in lung, but only after >48 h of exposure, and had no effect on kidney. The results suggest that the kidney metabolizes endogenous glucocorticoids, but the lung does not. Furthermore, the marked difference between lung and kidney responsiveness to glucocorticoids in beta- and gamma-ENaC expression suggests that factors other than steroids may be important in regulating functional ENaC expression during development.

Pregnancy

Phenotype

Corticosterone - administration & dosage

Glucocorticoids - administration & dosage

Kidney - embryology

RNA, Messenger - metabolism

Epithelial Sodium Channels

Kidney - metabolism

Dexamethasone - pharmacology

Corticotropin-Releasing Hormone - deficiency

Sodium Channels - metabolism

Glucocorticoids - physiology

Female

Lung - metabolism

Kidney - drug effects

Maternal-Fetal Exchange

Gene Expression Regulation, Developmental - drug effects

Mice, Knockout

Animals

Nuclease Protection Assays

Lung - drug effects

Lung - embryology

Mice

Sodium Channels - genetics

In Vitro Techniques

Details

Title: Subtitle: Endogenous and exogenous glucocorticoid regulation of ENaC mRNA expression in developing kidney and lung
Creators: Kenzo Nakamura - Department of Internal Medicine, University of Iowa College of Medicine and Veterans Affairs Medical Center, Iowa City 52242, USA
John B Stokes
Paul B McCray Jr
Resource Type: Journal article
Publication Details: American Journal of Physiology: Cell Physiology, Vol.283(3), pp.C762-772
DOI: 10.1152/ajpcell.00029.2002
PMID: 12176733
ISSN: 0363-6143
eISSN: 1522-1563
Grant note: DK-52617 / NIDDK NIH HHS DK-25295 / NIDDK NIH HHS HL-55006 / NHLBI NIH HHS
Language: English
Date published: 09/2002
Academic Unit: Microbiology and Immunology; Pulmonary Medicine; Stead Family Department of Pediatrics; Internal Medicine
Record Identifier: 9984093232902771

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