Gene Profiling of Testosterone-Regulated Genes in the Skeletal Muscle of Hiv-Infected Men Experiencing Weight Loss

ABSTRACT: 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

ORGANISM(S): Homo sapiens

PROVIDER: GSE5106 | GEO | 2007/08/29

SECONDARY ACCESSION(S): PRJNA95367

REPOSITORIES: GEO