title: Expression and cellular localization of the classical progesterone receptor in healthy and amyotrophic lateral sclerosis affected spinal cord.
abstract: OBJECTIVE
  Previous studies have suggested that elevated progesterone levels are associated with a slower disease course in amyotrophic lateral sclerosis (ALS). Given that the effects of progesterone are mediated in part by the classical progesterone receptor (PR), the expression and cellular localization of the A and B isoforms (PR-A and PR-B, respectively) of the PR in control (neuropathologically normal) and ALS-affected spinal cord (SC) were examined.
  
  
  METHODS
  Semi-quantitative RT-PCR, immunohistochemistry and immunofluorescence analyses of the cervical and lumbar SC of post-mortem ALS patients (n = 19) and control subjects (n = 10) were performed. Primers and antibodies used allowed the detection of both PR-A and PR-B isoforms together (PR-A+B) or PR-B isoform alone.
  
  
  RESULTS
  Lumbar PR-A+B and cervical PR-B mRNA expression were significantly higher in ALS than controls. In both ALS and controls, PR-A+B immunoreactivity (IR) was occasionally detected in motor neurons. In contrast, PR-A+B IR was prominent in axonal processes and vessels. This was more evident in nerve roots and large arteries in ALS compared with controls. Colocalization of PR-A+B with markers of neurons, axonal processes and vascular endothelium was also observed.
  
  
  CONCLUSIONS
  Evidence that both PR-A and PR-B isoforms are expressed in the human SC is provided, with some regional variation in isoform expression between ALS and controls. The IR was more prominent in nerve roots and large arteries in ALS, suggesting a potential role in the degenerative process.
authors.affiliation: Laboratory of Neuroendocrine Biochemistry, Instituto de Biología y Medicina Experimental - CONICET and School of Medicine, University of Buenos Aires, Buenos Aires, Argentina; Molecular Brain Research Group, Robarts Research Institute, Western University, London, ON, Canada.
authors.forename: G M
authors.initials: GM
authors.lastname: Gargiulo-Monachelli
authors.forename: D
authors.initials: D
authors.lastname: Campos-Melo
authors.forename: C A
authors.initials: CA
authors.lastname: Droppelmann
authors.forename: B A
authors.initials: BA
authors.lastname: Keller
authors.forename: C
authors.initials: C
authors.lastname: Leystra-Lantz
authors.forename: A F
authors.initials: AF
authors.lastname: De Nicola
authors.forename: M C
authors.initials: MC
authors.lastname: Gonzalez Deniselle
authors.forename: K
authors.initials: K
authors.lastname: Volkening
authors.forename: M J
authors.initials: MJ
authors.lastname: Strong
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009046:Motor Neurons / Q000378:metabolism* / Q000473:pathology; D011980:Receptors, Progesterone / Q000378:metabolism*; D013116:Spinal Cord / Q000378:metabolism* / Q000473:pathology; D013126:Spinal Nerve Roots / Q000378:metabolism / Q000473:pathology
chemical_list: D011980:Receptors, Progesterone
keywords: ALS; neuroprotection; progesterone; progesterone receptor; spinal cord