Transcriptional profiling of testosterone-regulated genes in the skeletal muscle of human immunodeficiency virus-infected men experiencing weight loss

Monty Montano, John N. Flanagan, Lan Jiang, Paola Sebastiani, Matthew Rarick, Nathan K LeBrasseur, Carl A. Morris, Ravi Jasuja, Shalender Bhasin

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Context: HIV-associated wasting and weight loss remain clinically significant concerns even in the era of potent antiretroviral therapy. Although androgen treatment increases muscle mass, the cell-intrinsic mechanisms engaged remain poorly understood. Objective: This study was an unbiased approach to identify expression profiles associated with testosterone treatment using genomewide microarray analysis of skeletal muscle biopsies. Design, Setting, and Participants: Forty-four HIV-positive men with weight loss were randomized to receive either 300 mg testosterone enanthate or placebo injections im weekly for 16 wk. Muscle biopsies were obtained at baseline and on treatment d 14. A subset of specimens was chosen for microarray analysis, with changes in selected genes confirmed by real-time PCR, Western blot analysis, and in vitro culture of muscle precursor cells. Results: Significantly greater gains in body mass (+2.05 and -1.07 kg, respectively; P = 0.003) and lean body mass by dual-energy x-ray absorptiometry (2.93 vs. 0.35 kg, respectively; P = 0.003) were observed in subjects treated with testosterone compared with placebo. Microarray analysis revealed up-regulation in genes involved in myogenesis and muscle protein synthesis, immune regulation, metabolic pathways, and chromatin remodeling. Representative genes were confirmed by real-time PCR and protein expression studies. In an independent analysis, gene networks that differentiate healthy young men from older men with sarcopenia had substantial overlap with those activated by testosterone treatment. Conclusions: These data provide new insights into the mechanisms of androgen action and have implications for both development of muscle biomarkers and anabolic therapies for wasting and sarcopenia.

Original languageEnglish (US)
Pages (from-to)2793-2802
Number of pages10
JournalJournal of Clinical Endocrinology and Metabolism
Volume92
Issue number7
DOIs
StatePublished - Jul 2007
Externally publishedYes

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Viruses
Muscle
Testosterone
Weight Loss
Skeletal Muscle
Genes
HIV
Microarrays
Microarray Analysis
Biopsy
Sarcopenia
Muscle Development
Androgens
Real-Time Polymerase Chain Reaction
Therapeutics
Placebos
Muscle Proteins
Biomarkers
Chromatin Assembly and Disassembly
Myoblasts

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

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Transcriptional profiling of testosterone-regulated genes in the skeletal muscle of human immunodeficiency virus-infected men experiencing weight loss. / Montano, Monty; Flanagan, John N.; Jiang, Lan; Sebastiani, Paola; Rarick, Matthew; LeBrasseur, Nathan K; Morris, Carl A.; Jasuja, Ravi; Bhasin, Shalender.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 92, No. 7, 07.2007, p. 2793-2802.

Research output: Contribution to journalArticle

Montano, Monty ; Flanagan, John N. ; Jiang, Lan ; Sebastiani, Paola ; Rarick, Matthew ; LeBrasseur, Nathan K ; Morris, Carl A. ; Jasuja, Ravi ; Bhasin, Shalender. / Transcriptional profiling of testosterone-regulated genes in the skeletal muscle of human immunodeficiency virus-infected men experiencing weight loss. In: Journal of Clinical Endocrinology and Metabolism. 2007 ; Vol. 92, No. 7. pp. 2793-2802.
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