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- Title
Testosterone stimulates muscle growth in association with PI3-K/Akt signaling in subjects with HIV.
- Authors
Koncarevic, Alan; Morris, Carl A.; Jasuja, Ravi; Flanagan, John; Montano, Monty; Bhasin, Shalender; LeBrasseur, Nathan K.
- Abstract
Recent evidence suggests androgens increase lean body mass and strength in subjects with HIV-associated wasting. The molecular basis for the anabolic effects of androgens in skeletal muscle, however, remain poorly understood. Given the key role of PI3-K/Akt signaling in the control of protein synthesis and degradation, we tested the hypothesis that testosterone (T) mediates protein accretion in the muscle of subjects with HIV by regulation of this pathway. In 44 HIV+ men, 16 wks of T (300mg/wk) increased lean body mass (2.93 kgs, p < 0.03). Comparison of muscle biopsies obtained at baseline and 14 days after. T demonstrated significant increases in the phosphorylation of Akt and mTOR (n = 10). Examination of their downstream effectors, S6K, S6, 4EBP-1, and elF4G, revealed increased phosphorylation consistent with the activation of protein translation. Preliminary findings also suggest that mRNA levels of muscle-specific E3 ligases involved in protein degradation, MAFbxl and MuRF1, are significantly downregulated in T treated subjects. These findings support that T may in part mediate its anabolic effects via activation of PI3-kinase/Akt signaling. Ongoing experiments in human primary myoblasts are being conducted to further elucidate mechanisms of T action.
- Subjects
ANDROGENS; MUSCLES; PROTEIN synthesis; TESTOSTERONE; HIV-positive persons; HUMAN body composition; LIGASES; MYOBLASTS
- Publication
FASEB Journal, 2007, Vol 21, Issue 6, pA946
- ISSN
0892-6638
- Publication type
Article