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Glucocorticoid receptor is indispensable for mineralocorticoid receptor‐dependent induction of colonic epithelial Na+ channels
Author(s) -
Bergann Theresa,
Fromm Anja,
Borden Steffen A,
Fromm Michael,
Schulzke Joerg D
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.1039.20
Subject(s) - epithelial sodium channel , glucocorticoid receptor , mineralocorticoid receptor , sgk1 , mineralocorticoid , glucocorticoid , endocrinology , receptor , medicine , aldosterone , agonist , antiglucocorticoid , chemistry , transcription factor , signal transduction , biology , microbiology and biotechnology , sodium , gene , biochemistry , organic chemistry
Introduction In the colon, electrogenic sodium absorption is controlled by the epithelial Na+ channel (ENaC). We characterized the interplay of glucocorticoids and mineralocorticoids in ENaC signaling which is only poorly understood due to the lack of epithelial cell lines co‐expressing functional glucocorticoid (GR) and mineralocorticoid receptors (MR). Methods Interplay of the two receptors was studied in the highly differentiated, human colon cell line HT‐29/B6‐GR/MR equipped with the complete receptor repertoire of both GR and MR due to stable transfection. Results In contrast to HT‐29/B6 cells solely expressing the MR, HT‐29/B6‐GR/MR cells displayed a physiological response to aldosterone regarding ENaC induction after a pre‐incubation step with the GR agonist dexamethasone. Resulting from cooperative effects between the activated GR and the MR, MR protein levels were elevated and MR‐dependent transcription of ENaC subunits β and γ was increased. As an additional mechanism involved, transcription of SGK‐1 (serum‐ and glucocorticoid‐induced kinase 1) and GILZ (glucocorticoid‐induced leucin zipper) ‐ both essential for the rise in apical ENaC levels ‐ were also augmented by the activated MR. Conclusion After generating a new GR/MR colonic cell model we showed that GR expression and GR pre‐stimulation were indispensable for the MR‐dependent induction of ENaC.