The role of testosterone of the histone deacetylase system
Lee, Daniel Chang-Kyou
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The goal of this study is to examine testosterone's action on the androgen sensitive skeletal muscle levator ani. The primary purposes were to examine if testosterone deprivation induces changes in histone deacetylase (HDAC) distribution and in HDACs and myogenin level during muscle atrophy, and if testosterone supplementation rescues these changes. Sexually mature male mice were castrated, and treated with and without testosterone. Sham operated mice served as control. All mice were sacrificed 7 and 14 days days post testosterone proprionate (Tp) administration. Blood was collected to quantify serum testosterone concentrations while the levator ani was removed and weighed. Muscle sections were processed for immunofluorescence and stained for HDACs and acetylcholine receptors. Furthermore, western blot and qPCR analysis was done on the samples taken from the mice. Myogenin and HDAC levels were quantified by Western blots and qPCR. Data analysis revealed statistically significant differences in the Western blot and qPCR results comparing the Sham, Cast and Cast Tp experimental groups. With at least a P less than .01 significantly lower levels of HDACs and Myogenin were seen in the Sham and the Cast Tp groups as compared to the Cast group. Immunofluorescence data on HDAC4 distribution at the level of the neuromuscular junction revealed no statistically significant differences in the means of all groups but the trend that appeared was similar to the expected result of Sham and Cast Tp being higher than Cast. The findings of the study from the qPCR and Western blot analysis support the finding that testosterone significantly reduces the levels of class II HDACs as well as myogenin in castrated mice, to levels comparable to Sham mice. We also find that testosterone supplementation redistribute the HDACs near the neuromuscular junction, again similar in phenotypic profile of the Sham group. These data support the growing importance of HDACs in determining the biochemical pathway that testosterone utilizes to induce muscle anabolism.
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