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| Status |
Public on Jul 01, 2009 |
| Title |
Effects of testosterone on dexamethasone-induced changes in gene expression in gastrocnemius muscles from male rats |
| Organism |
Rattus norvegicus |
| Experiment type |
Expression profiling by array
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| Summary |
Glucocorticoids are a well recognized and common cause of muscle atrophy. Glucocorticoid-induced atrophy can be prevented by testosterone, but the molecular mechanisms underlying such protection have not been described. Thus, the global effects of testosterone on dexamethasone-induced changes in gene expression were evaluated in rat gastrocnemius muscle using Affymetrix 230_2 DNA microarrays. Gene expression was analyzed after 7 days administration of dexamethasone, dexamethasone plus testosterone, or vehicle. Effects of these agents on weights of gastrocnemius muscles from these animals has been reported (1. Zhao W, Pan J, Zhao Z, Wu Y, Bauman WA, and Cardozo CP. Testosterone protects against dexamethasone-induced muscle atrophy, protein degradation and MAFbx upregulation. J Steroid Biochem Mol Biol 110: 125-129, 2008.) Dexamethasone changed expression of 876 probe sets by at least 2-fold, of which 474 probe sets were changed by at least two fold in the opposite direction in the dexamethasone plus testosterone group (genes in opposition). Major biological themes represented by genes in opposition included IGF-1 signaling, protein synthesis, myogenesis and muscle development, and ubiquitin conjugases and ligases. Testosterone blocked increased expression of DDIT4 and eIF4EBP1, FOXO1 and of the p85 regulatory subunit of the IGF-1 receptor, while preventing decreased expression of IRS-1. Testosterone blocked decreased expression of LXR and suppressed upregulation of C/EBP beta and delta. Testosterone prevented increase expression of Cdkn1A (p21) and decrease expression of cyclins B and D, as well as many other changes that would be expected to reduce cell cycle progression. Testosterone prevented increased expression of muscle development factors Csrp3 and Mbn1 and blocked reduced expression of Wnt4. These data suggest that testosterone blocks multiple changes in gene expression that, collectively, would otherwise downregulate molecular signals that promote protein synthesis and muscle hypertrophy and that stimulate muscle protein catabolism.
Keywords: Evaluate drug effects at a single time point
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| Overall design |
Rats (250 g males) were administered dexamethasone (0.7 mg/kg/day) alone or with testosterone (20 mg/kg/day) dissolved in vehicle (propylene glycol) by continuous infusion (Alzet pumps) for 7 days. Control animals were administered vehicle only. Gene expression was compared among the 3 groups at 7 days using one chip per animal, 3 animals per group.
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| Contributor(s) |
Cardozo C, Wu Y |
| Citation(s) |
20032058 |
| Submission date |
Jul 30, 2008 |
| Last update date |
Jul 31, 2017 |
| Contact name |
christopher p cardozo |
| E-mail(s) |
chris.cardozo@mssm.edu
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| Phone |
718-584-9000
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| Organization name |
Bronx VA Medical Center
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| Department |
CMSCI
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| Lab |
Room 3F-35
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| Street address |
130 West Kingsbridge Road
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| City |
Bronx |
| State/province |
NY |
| ZIP/Postal code |
10468 |
| Country |
USA |
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| Platforms (1) |
| GPL1355 |
[Rat230_2] Affymetrix Rat Genome 230 2.0 Array |
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| Samples (9)
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| GSM309171 |
Gastroc m. Drug Treatment 7 Days Control 1 |
| GSM309172 |
Gastroc m. Drug Treatment 7 days Control 2 |
| GSM309173 |
Gastroc m. Drug Treatment 7 Days Control 3 |
| GSM309174 |
Gastroc m. Drug Treatment 7 Days Dex 1 |
| GSM309175 |
Gastroc m. Drug Treatment 7 Days Dex 2 |
| GSM309176 |
Gastroc m. Drug Treatment 7 Days Dex 3 |
| GSM309177 |
Gastroc m. Drug Treatment 7 Days DexTs 1 |
| GSM309178 |
Gastroc m. Drug Treatment 7 Days DexTs 2 |
| GSM309179 |
Gastroc m. Drug Treatment 7 Days DexTs 3 |
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| Relations |
| BioProject |
PRJNA113591 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE12296_RAW.tar |
22.8 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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