This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The primary objective of this project is to determine if testosterone replacement of HIV-infected men with weight loss and low testosterone levels will improve objective measures of physical function, perceptions of physical function and body image. A second objective is to determine if testosterone replacement improves lower extremity power and fatigability. A third objective is to elucidate the mechanisms by which testosterone increases muscle mass. Hypothesis This placebo-controlled, randomized, double-blind, parallel-group, clinical trial will test the following hypotheses: 1. Testosterone replacement of HIV-infected men with low testosterone levels and weight loss will be associated with greater increases in measures of physical function that those associated with placeb0-treatment. 2. Testosterone replacement will be associated with greater improvements in measures of muscle performance such as muscle power and fatigability, as well as maximal voluntary strength than those associated with placebo. 3. Testosterone-inducted gains in measures of muscle performance and physical function will be associated with significant improvements in perceptions of physical function and body image. 4. Testosterone increases fat-free mass by upregulation of muscle IGF-I mRNA and protein, and downregulation of myostatin mRNA and protein. Testosterone dose does not affect measures of muscle protein breakdown as measured by proteasome and ubiquitin mRNA concentations.
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