An ERRbeta/gamma agonist modulates GRalpha expression, and glucocorticoid responsive gene expression in skeletal muscle cells

Wang, Shu-Ching Mary, Myers, Stephen, Dooms, Cedric, Capon, Robert and Muscat, George E. O. (2010) An ERRbeta/gamma agonist modulates GRalpha expression, and glucocorticoid responsive gene expression in skeletal muscle cells. Molecular and Cellular Endocrinology, 315 1-2: 146-152. doi:10.1016/j.mce.2009.07.012


Author Wang, Shu-Ching Mary
Myers, Stephen
Dooms, Cedric
Capon, Robert
Muscat, George E. O.
Title An ERRbeta/gamma agonist modulates GRalpha expression, and glucocorticoid responsive gene expression in skeletal muscle cells
Formatted title
An ERRβ/γ agonist modulates GRα expression, and glucocorticoid responsive gene expression in skeletal muscle cells
Journal name Molecular and Cellular Endocrinology   Check publisher's open access policy
ISSN 0303-7207
1872-8057
Publication date 2010-02-05
Year available 2009
Sub-type Article (original research)
DOI 10.1016/j.mce.2009.07.012
Volume 315
Issue 1-2
Start page 146
End page 152
Total pages 7
Editor I. T. Huhtaniemi
Place of publication Shannon, Ireland
Publisher Elsevier Ireland
Collection year 2011
Language eng
Subject C1
920106 Endocrine Organs and Diseases (excl. Diabetes)
110306 Endocrinology
060405 Gene Expression (incl. Microarray and other genome-wide approaches)
060104 Cell Metabolism
Formatted abstract
Estrogen-related receptors (ERRs) are constitutively active orphan nuclear receptors. Natural ligands have not been identified, however, recent reports have demonstrated the synthetic phenolic acyl hydrazone, GSK4716, functions as a selective ERRβ/γ agonist. We demonstrate that ERRβ is transiently induced, and ERRγ is dramatically induced (and accumulates) in a differentiation-dependent manner in skeletal muscle cells. Treatment of differentiated skeletal muscle cells with the ERRβ/γ agonist (GSK4716) produced a significant increase in the expression of GRα (isoform D) protein. Quantitative RT-PCR (Q-RT-PCR) analysis after treatment with GSK4716, revealed induction of the mRNAs encoding the glucocorticoid receptor (GR), 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), the enzyme that converts inactive cortisone to cortisol and hexose-6-phosphate dehydrogenase expression (H6PDH) that stimulates oxoreduction by 11β-HSD1. Candidate based expression profiling also demonstrated the mRNAs encoding characterized GR target genes, including C/EBP, ApoD and Monoamine oxidase-A (MAO-A) are induced in GSK4716 treated cells. In concordance with these observations, siRNA-mediated suppression of the mRNA encoding ERRγ (but not ERRα and β) attenuated the expression of mRNAs encoding GR, 11βHSD1 and GR target gene(s). Similarly, treatment with the ERRγ (and ERα) antagonist diethylstilbestrol (DES) suppressed glucocorticoid responsive gene expression in skeletal muscle cells. Interestingly, we observed that GSK4716 trans-activated GRE-TK-LUC in a GR-dependent manner. This study highlights the regulatory crosstalk between ERRγ and GR signaling in skeletal muscle cells, and suggests the ERRγ agonist modulates the expression of critical genes that control GR signaling and glucocorticoid sensitive gene expression.
© 2009 Elsevier Ireland Ltd. All rights
Keyword Estrogen-related receptor
Glucocorticoid receptor
GSK4716
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Available online 23 July 2009.

Document type: Journal Article
Sub-type: Article (original research)
Collections: 2010 Higher Education Research Data Collection
Institute for Molecular Bioscience - Publications
 
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Created: Mon, 22 Feb 2010, 11:11:42 EST by Susan Allen on behalf of Institute for Molecular Bioscience