Session: MON 355-388-Sex Hormone Receptor Action & Reaction
Poster Board MON-372
Methods: We used the Hershberger castration assay in rodents. 2-month old male mice were castrated and treated with testosterone propionate in corn oil (vehicle) for 7, 14 and 43 days, or with vehicle alone. Sham-operated, vehicle-treated mice, served as control.
Results: Castrated mice showed loss of the mass of both the high androgen-responder levator ani muscle and the low androgen-responder triceps muscle. Loss of the mass of the levator ani muscle was associated with increased expression of Hdac4 and Hdac5, as well as of the nuclear co-repressor NCoR1. This pattern of gene expression in castrated mice was coupled with upregulation of myogenin and Mef2C, as well as of the two main muscle E3 ubiquitin ligases MuRF1 and MAFbx. Interestingly, the levator ani muscle of castrated mice showed strongly reduced level of Hdac4 at the neuromuscular junction, and more diffused staining for Hdac4 in the sarcoplasm. A similar pattern was found for Hdac5 and for Hdca3, the physiological binding partner of Hdac4. In addition, castrated mice showed testosterone-mediated modulation of Dach2 and mir-206 gene expression. Finally, the levator animuscle of castrated mice showed reduced level of Fgf10 and Fgf binding protein 1 (FgfBP1), two positive regulators of synapse formation. Testosterone supplementation in castrated mice rescued all these changes.
Conclusion: Testosterone deprivation mimics the effect of muscle denervation on specific proteins involved in the neuromuscular structure and synapse formation. These data indicate that the anabolic effect of testosterone on the skeletal muscle might be mediated by the signaling regulated by neuromuscular activation and by the HDACs, and suggest new therapeutic approaches for neuromuscular diseases.
Nothing to Disclose: CS, DL, NLS, GT, HJ, RJ, SB
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