Journal
MOLECULAR AND CELLULAR ENDOCRINOLOGY
Volume 302, Issue 1, Pages 18-25Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.mce.2008.12.008
Keywords
Glucocorticoid receptor; Mineralocorticoid receptor; Dexamethasone; Aldosterone; Nuclear receptor
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Funding
- Kochi University President's Discretionary
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The mineralocorticoid receptor (MR) plays an important functional role in the central nervous system; however, the molecular mechanism of MR-dependent gene expression is not entirely clear. In this study, we examined the MR-dependent transcriptional regulation using a human neuronal cell line BE(2)C and an MR/GR-dependent reporter gene (HRE-luciferase) in vitro. Western blot analysis revealed that the cell line expresses MR but not glucocorticoid receptor (GR). In this experimental condition, unexpectedly, the MR-specific ligand aldosterone did not induce HRE-dependent transcription in a native or MR-overexpressed condition, whereas significant transcriptional induction by aldosterone was observed when the GR was co-expressed. The effect of aldosterone was completely inhibited by the MR antagonist spironolactone, indicating an MR-dependent effect. We found similar results in T84 colonic cells expressing neither MR nor GR, such that the aldosterone effect was obtained only when both receptors were co-expressed. The co-operative effect of GR was not obvious with the dimer-deficient mutant GR. Finally, the above findings were reproducible with different promoters containing HIRE such as ENaC and MMTV. These results suggest that GR plays an indispensable role in MR-dependent transcription, possibly by forming a MR/GR heterodimer or by acting as a co-activator of MR/MR homodimer. (C) 2008 Elsevier Ireland Ltd. All rights reserved.
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