Androgen-dependent impairment of myogenesis in spinal and bulbar muscular atrophy

Adriana Malena, Maria Pennuto, Caterina Tezze, Giorgia Querin, Carla D'Ascenzo, Vincenzo Silani, Giovanna Cenacchi, Annarita Scaramozza, Silvia Romito, Lucia Morandi, Elena Pegoraro, Aaron P. Russell, Gianni Sorarù, Lodovica Vergani

Research output: Contribution to journalArticlepeer-review


Spinal and bulbar muscular atrophy (SBMA) is an inherited neuromuscular disease caused by expansion of a polyglutamine (polyQ) tract in the androgen receptor (AR). SBMA is triggered by the interaction between polyQ-AR and its natural ligands, testosterone and dihydrotestosterone (DHT). SBMA is characterized by the loss of lower motor neurons and skeletal muscle fasciculations, weakness, and atrophy. To test the hypothesis that the interaction between polyQ-AR and androgens exerts cell-autonomous toxicity in skeletal muscle, we characterized the process of myogenesis and polyQ-AR expression in DHT-treated satellite cells obtained from SBMA patients and age-matched healthy control subjects. Treatment with androgens increased the size and number of myonuclei in myotubes from control subjects, but not from SBMA patients. Myotubes from SBMA patients had a reduced number of nuclei, suggesting impaired myotube fusion and altered contractile structures. The lack of anabolic effects of androgens on myotubes from SBMA patients was not due to defects in myoblast proliferation, differentiation or apoptosis. DHT treatment of myotubes from SBMA patients increased nuclear accumulation of polyQ-AR and decreased the expression of interleukin-4 (IL-4) when compared to myotubes from control subjects. Following DHT treatment, exposure of myotubes from SBMA patients with IL-4 treatment rescued myonuclear number and size to control levels. This supports the hypothesis that androgens alter the fusion process in SBMA myogenesis. In conclusion, these results provide evidence of an androgen-dependent impairment of myogenesis in SBMA that could contribute to disease pathogenesis.

Original languageEnglish
Pages (from-to)109-121
Number of pages13
JournalActa Neuropathologica
Issue number1
Publication statusPublished - Jul 2013


  • Androgen receptor
  • Dihydrotestosterone
  • Interleukin-4
  • Myogenesis
  • Spinal and bulbar muscular atrophy

ASJC Scopus subject areas

  • Clinical Neurology
  • Pathology and Forensic Medicine
  • Cellular and Molecular Neuroscience


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