Expression of the pituitary stem/progenitor marker GFRα2 in human pituitary adenomas and normal pituitary

Nestoras Mathioudakis, Ram Sundaresh, Alexandra Larsen, William Ruff, Jennifer Schiller, Hugo Guerrero-Cázares, Peter Burger, Roberto Salvatori, Alfredo Quiñones-Hinojosa

Research output: Contribution to journalArticle

Abstract

Purpose: 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. Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)31-41
Number of pages11
JournalPituitary
Volume18
Issue number1
DOIs
StatePublished - Feb 1 2015

Keywords

  • Adenoma
  • GFRα2
  • Glial cell-line derived neurotrophic factor receptor alpha 2
  • Gonadotropinoma
  • Progenitor
  • Stem

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Fingerprint Dive into the research topics of 'Expression of the pituitary stem/progenitor marker GFRα2 in human pituitary adenomas and normal pituitary'. Together they form a unique fingerprint.

  • Cite this

    Mathioudakis, N., Sundaresh, R., Larsen, A., Ruff, W., Schiller, J., Guerrero-Cázares, H., Burger, P., Salvatori, R., & Quiñones-Hinojosa, A. (2015). Expression of the pituitary stem/progenitor marker GFRα2 in human pituitary adenomas and normal pituitary. Pituitary, 18(1), 31-41. https://doi.org/10.1007/s11102-014-0553-1