title: Testosterone treatment fails to accelerate disease in a transgenic mouse model of spinal and bulbar muscular atrophy.
abstract: Evidence from multiple animal models demonstrates that testosterone plays a crucial role in the progression of symptoms in spinal and bulbar muscular atrophy (SBMA), a condition that results in neurodegeneration and muscle atrophy in affected men. Mice bearing a transgene encoding a human androgen receptor (AR) that contains a stretch of 112 glutamines (expanded polyglutamine tract; AR112Q mice) reproduce several aspects of the human disease. We treated transgenic male AR112Q mice with testosterone for 6 months. Surprisingly, testosterone treatment of AR112Q males did not exacerbate the disease. Although transgenic AR112Q males exhibited functional deficits when compared with non-transgenics, long-term testosterone treatment had no effect on motor function. Testosterone treatment also failed to affect cellular markers of disease, including inclusion formation (the accumulation of large nuclear aggregates of mutant AR protein) and levels of unphosphorylated neurofilament heavy chain. These data suggest that the mechanism of disease in SBMA saturates at close to endogenous hormone levels and that individuals with SBMA who take, or have taken, testosterone for its putative therapeutic properties are unlikely to suffer adverse effects.
authors.affiliation: Department of Biochemistry and Molecular Biology, Thomas Jefferson University, Philadelphia, PA 19107, USA.
authors.forename: Erica S
authors.initials: ES
authors.lastname: Chevalier-Larsen
authors.forename: Diane E
authors.initials: DE
authors.lastname: Merry
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D055534:Bulbo-Spinal Atrophy, X-Linked / Q000188:drug therapy* / Q000473:pathology*; D004195:Disease Models, Animal; D018450:Disease Progression; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D010641:Phenotype; D013739:Testosterone / Q000627:therapeutic use*; D017211:Treatment Failure
chemical_list: D015415:Biomarkers; D013739:Testosterone