title: Expression of the pituitary stem/progenitor marker GFRα2 in human pituitary adenomas and normal pituitary.
abstract: OBJECTIVE
  Recent studies suggest that adult pituitary stem cells may play a role in pituitary tumorigenesis. We sought to explore whether the Glial cell-line derived neurotrophic factor receptor alpha 2 (GFRα2), a recently described pituitary stem/progenitor marker, might be differentially expressed in pituitary adenomas versus normal pituitary.
  
  
  METHODS
  The expression of GFRα2 and other members of the GFR receptor family (GFRα1, α3, α4) were analyzed using RT-PCR, western blot, and immunohistochemistry in 39 pituitary adenomas, 14 normal pituitary glands obtained at autopsy, and cDNA from 3 normal pituitaries obtained commercially.
  
  
  RESULTS
  GFRα2 mRNA was ~2.6 fold under-expressed in functioning adenomas (p < 0.01) and ~3.5 fold over-expressed in non-functioning adenomas (NFAs) (p < 0.05) compared to normal pituitary. Among NFAs, GFRα2 was significantly over-expressed (~5-fold) in the gonadotropinoma subtype only (p < 0.05). GFRα2 protein expression appeared to be higher in most NFAs, although there was heterogeneity in protein expression in this group. GFRα2 protein expression appeared consistently lower in functioning adenomas by IHC and western blot. In normal pituitary, GFRα2 was localized in Rathke's remnant, the putative pituitary stem cell niche, and in corticotropes.
  
  
  CONCLUSIONS
  Our results suggest that the pituitary stem cell marker GFRα2 is under-expressed in functioning adenomas and over-expressed in NFAs, specifically gonadotropinomas. Further studies are required to elucidate whether over-expression of GFRα2 in gonadotropinomas might play a role in pituitary tumorigenesis.
authors.affiliation: Division of Endocrinology, Diabetes, and Metabolism, Johns Hopkins University School of Medicine, 1830 E. Monument Street, Suite 333, Baltimore, MD, 21287, USA, nmathio1@jhmi.edu.
authors.forename: Nestoras
authors.initials: N
authors.lastname: Mathioudakis
authors.forename: Ram
authors.initials: R
authors.lastname: Sundaresh
authors.forename: Alexandra
authors.initials: A
authors.lastname: Larsen
authors.forename: William
authors.initials: W
authors.lastname: Ruff
authors.forename: Jennifer
authors.initials: J
authors.lastname: Schiller
authors.forename: Hugo
authors.initials: H
authors.lastname: Guerrero-Cázares
authors.forename: Peter
authors.initials: P
authors.lastname: Burger
authors.forename: Roberto
authors.initials: R
authors.lastname: Salvatori
authors.forename: Alfredo
authors.initials: A
authors.lastname: Quiñones-Hinojosa
mesh_terms: D000236:Adenoma / Q000503:physiopathology*; D000328:Adult; D000368:Aged; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D010902:Pituitary Gland / Q000378:metabolism* / Q000503:physiopathology*; D010911:Pituitary Neoplasms / Q000503:physiopathology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055815:Young Adult
chemical_list: D051100:Glial Cell Line-Derived Neurotrophic Factor