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| Status |
Public on Aug 29, 2007 |
| Title |
Gene Profiling of Testosterone-Regulated Genes in the Skeletal Muscle of Hiv-Infected Men Experiencing Weight Loss |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Context: Although androgen treatment increases muscle mass in HIV-infected men, the underlying mechanisms are poorly understood. Analysis of genome-wide microarray data obtained from skeletal muscle biopsies can be used to profile androgen-regulated pathways.
Objective: To identify genes and pathways associated with testosterone treatment and myogenesis in the context of HIV-infected men using genome-wide microarray analysis of skeletal muscle biopsies.
Results: A significant weight gain was observed in subjects treated with testosterone compared to placebo (+2.05 kgs and –1.07 kgs, respectively; P = 0.003) as well as gains in DEXA lean
mass (2.93 kgs vs. 0.35 kgs, respectively; P = 0.003). Microarray expression profiles and RTPCR validation of RNA after 14 days of treatment indicated that several gene sets including
transcriptional control, myogenesis, adipogenesis, insulin signaling, apoptosis, cell cycle, chromatin remodeling, and stress response genes were differentially expressed with testosterone treatment. Protein expression analysis of myogenic differentiation and protein synthesis markers (MyoD, Myogenin, phosphorylated p38 MAPK and phosphorylated AKT) in muscle biopsies and skeletal muscle cells treated with DHT confirmed that testosterone engages
a network of pro-myogenic genes.
Conclusions: Testosterone-associated gain in muscle mass in HIV-infected men engaged a network of regulatory pathways involved in broad transcriptional control, myogenesis, insulin signaling, chromatin remodeling, and stress response. Further evaluation of precise signaling intermediates within androgen regulated pathways may help to better define improvements in muscle mass, both in healthy and HIV infected patients.
Keywords: Dose Response, Myogenesis
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| Overall design |
Design, Setting, and Participants: 44 HIV+ men with weight loss were randomized to receive either 300mg testosterone enanthate or placebo injections IM weekly for 16 weeks. Muscle
biopsies were obtained at baseline and on treatment day 14. A random subset of specimens was chosen for microarray analysis; changes in selected genes were confirmed by reverse transcriptase - polymerase chain reaction (RT-PCR), and western blot analysis. Human skeletal
myogenic precursor cells (SkMCs) were cultured in vitro in the presence of dihydrotestosterone (DHT) to evaluate activation of myogenic protein expression.
Main outcome measures: Relative RNA levels in skeletal muscle biopsies were measured by expression profiling with microarrays and expression levels were validated in samples using quantitative RT-PCR. Further confirmation of changes in key myogenic biomarkers was obtained in DHT treated SkMCs.
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| Contributor(s) |
Montano M, Flanagan JN, Jiang L, Sebastiani P, Rarick M, LeBrasseur NK, Morris CA, Jasuja R, Bhasin S |
| Citation(s) |
17440010 |
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| Submission date |
Jun 20, 2006 |
| Last update date |
Dec 06, 2018 |
| Contact name |
Monty Montano |
| E-mail(s) |
mmontano@bu.edu
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| Phone |
617 414-4806
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| Fax |
617 414-3561
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| URL |
http://www.bmc.org/HIV-AIDS/MontyMontano.htm
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| Organization name |
Boston Medical Center
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| Department |
Medicine
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| Lab |
Center for HIV-1/AIDS Care and Research
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| Street address |
650 Albany Street, Bldg X, room 640
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| City |
Boston |
| State/province |
MA |
| ZIP/Postal code |
02118 |
| Country |
USA |
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| Platforms (1) |
| GPL571 |
[HG-U133A_2] Affymetrix Human Genome U133A 2.0 Array |
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| Samples (19)
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| GSM113921 |
Placebo treated, HIV-1 positive male, day 14 (1) |
| GSM115323 |
Placebo treated, HIV-1 positive male, day 14 (2) |
| GSM115325 |
Placebo treated, HIV-1 positive male, day 14 (3) |
| GSM115326 |
Placebo treated, HIV-1 positive male, day 14 (4) |
| GSM115327 |
Placebo treated, HIV-1 positive male, day 14 (5) |
| GSM115328 |
Placebo treated, HIV-1 positive male, day 14 (6) |
| GSM115329 |
Placebo treated, HIV-1 positive male, day 14 (7) |
| GSM115330 |
Placebo treated, HIV-1 positive male, day 14 (8) |
| GSM115331 |
Placebo treated, HIV-1 positive male, day 14 (9) |
| GSM115332 |
Testosterone treated, HIV-1 positive male, day 14 (1) |
| GSM115333 |
Testosterone treated, HIV-1 positive male, day 14 (2) |
| GSM115334 |
Testosterone treated, HIV-1 positive male, day 14 (3) |
| GSM115335 |
Testosterone treated, HIV-1 positive male, day 14 (4) |
| GSM115336 |
Testosterone treated, HIV-1 positive male, day 14 (5) |
| GSM115337 |
Testosterone treated, HIV-1 positive male, day 14 (6) |
| GSM115338 |
Testosterone treated, HIV-1 positive male, day 14 (7) |
| GSM115339 |
Testosterone treated, HIV-1 positive male, day 14 (8) |
| GSM115340 |
Testosterone treated, HIV-1 positive male, day 14 (9) |
| GSM115341 |
Testosterone treated, HIV-1 positive male, day 14 (10) |
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| Relations |
| BioProject |
PRJNA95367 |
| Supplementary data files not provided |
| Processed data included within Sample table |
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