title: Mutant androgen receptor accumulation in spinal and bulbar muscular atrophy scrotal skin: a pathogenic marker.
abstract: OBJECTIVE
  Spinal and bulbar muscular atrophy (SBMA) is a hereditary motor neuron disease caused by the expansion of a polyglutamine tract in the androgen receptor (AR). The nuclear accumulation of mutant AR is central to the pathogenesis of SBMA. Androgen deprivation with leuprorelin inhibits mutant AR accumulation, resulting in rescue of neuronal dysfunction in a mouse model of SBMA. This study aimed to investigate whether mutant AR accumulation in the scrotal skin is an appropriate biomarker of SBMA.
  
  
  METHODS
  Immunohistochemistry of both scrotal skin and the spinal cord was performed on five autopsied SBMA cases. Neurological severity and scrotal skin findings were studied in another 13 patients. Five other patients received subcutaneous injections of leuprorelin and underwent scrotal skin biopsy.
  
  
  RESULTS
  The degree of mutant AR accumulation in scrotal skin epithelial cells tended to be correlated with that in the spinal motor neurons in autopsy specimens, and it was well correlated with CAG repeat length and inversely correlated with the amyotrophic lateral sclerosis functional scale. Leuprorelin treatment inhibited mutant AR protein accumulation in the scrotal skin of SBMA patients.
  
  
  CONCLUSIONS
  These observations suggest that scrotal skin biopsy findings are a potent pathogenic marker of SBMA and can be a surrogate end point in therapeutic trials.
authors.affiliation: Department of Neurology, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya, Japan.
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Banno
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Adachi
authors.forename: Masahisa
authors.initials: M
authors.lastname: Katsuno
authors.forename: Keisuke
authors.initials: K
authors.lastname: Suzuki
authors.forename: Naoki
authors.initials: N
authors.lastname: Atsuta
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Watanabe
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Tanaka
authors.forename: Manabu
authors.initials: M
authors.lastname: Doyu
authors.forename: Gen
authors.initials: G
authors.lastname: Sobue
mesh_terms: D000328:Adult; D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage; D002452:Cell Count / Q000379:methods; D003402:Creatine Kinase / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D016729:Leuprolide / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009134:Muscular Atrophy, Spinal / Q000235:genetics* / Q000473:pathology*; D009154:Mutation; D010455:Peptides / Q000378:metabolism; D011944:Receptors, Androgen / Q000235:genetics* / Q000378:metabolism; D012611:Scrotum / Q000473:pathology*; D012867:Skin / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology; D013223:Statistics as Topic; D013997:Time Factors
chemical_list: D018931:Antineoplastic Agents, Hormonal; D010455:Peptides; D011944:Receptors, Androgen; C097188:polyglutamine; D003402:Creatine Kinase; D016729:Leuprolide