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 Cazares, Peter Burger, Roberto Salvatori, Alfredo Quinones-Hinojosa

Research output: Contribution to journalArticle

8 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Pituitary Neoplasms
Adenoma
Carcinogenesis
Glial Cell Line-Derived Neurotrophic Factor Receptors
Western Blotting
Stem Cell Niche
Proteins
Adult Stem Cells
Pituitary Gland
Autopsy
Stem Cells
Complementary DNA
Immunohistochemistry
Polymerase Chain Reaction
Messenger RNA

Keywords

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

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism
  • Medicine(all)

Cite this

Expression of the pituitary stem/progenitor marker GFRα2 in human pituitary adenomas and normal pituitary. / Mathioudakis, Nestoras; Sundaresh, Ram; Larsen, Alexandra; Ruff, William; Schiller, Jennifer; Guerrero Cazares, Hugo; Burger, Peter; Salvatori, Roberto; Quinones-Hinojosa, Alfredo.

In: Pituitary, Vol. 18, No. 1, 01.02.2015, p. 31-41.

Research output: Contribution to journalArticle

Mathioudakis, Nestoras ; Sundaresh, Ram ; Larsen, Alexandra ; Ruff, William ; Schiller, Jennifer ; Guerrero Cazares, Hugo ; Burger, Peter ; Salvatori, Roberto ; Quinones-Hinojosa, Alfredo. / Expression of the pituitary stem/progenitor marker GFRα2 in human pituitary adenomas and normal pituitary. In: Pituitary. 2015 ; Vol. 18, No. 1. pp. 31-41.
@article{77a143f61e7e42b39bac6c6dc3743bd3,
title = "Expression of the pituitary stem/progenitor marker GFRα2 in human pituitary adenomas and normal pituitary",
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.",
keywords = "Adenoma, GFRα2, Glial cell-line derived neurotrophic factor receptor alpha 2, Gonadotropinoma, Progenitor, Stem",
author = "Nestoras Mathioudakis and Ram Sundaresh and Alexandra Larsen and William Ruff and Jennifer Schiller and {Guerrero Cazares}, Hugo and Peter Burger and Roberto Salvatori and Alfredo Quinones-Hinojosa",
year = "2015",
month = "2",
day = "1",
doi = "10.1007/s11102-014-0553-1",
language = "English (US)",
volume = "18",
pages = "31--41",
journal = "Pituitary",
issn = "1386-341X",
publisher = "Kluwer Academic Publishers",
number = "1",

}

TY - JOUR

T1 - Expression of the pituitary stem/progenitor marker GFRα2 in human pituitary adenomas and normal pituitary

AU - Mathioudakis, Nestoras

AU - Sundaresh, Ram

AU - Larsen, Alexandra

AU - Ruff, William

AU - Schiller, Jennifer

AU - Guerrero Cazares, Hugo

AU - Burger, Peter

AU - Salvatori, Roberto

AU - Quinones-Hinojosa, Alfredo

PY - 2015/2/1

Y1 - 2015/2/1

N2 - 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.

AB - 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.

KW - Adenoma

KW - GFRα2

KW - Glial cell-line derived neurotrophic factor receptor alpha 2

KW - Gonadotropinoma

KW - Progenitor

KW - Stem

UR - http://www.scopus.com/inward/record.url?scp=84931955459&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84931955459&partnerID=8YFLogxK

U2 - 10.1007/s11102-014-0553-1

DO - 10.1007/s11102-014-0553-1

M3 - Article

C2 - 24402129

AN - SCOPUS:84931955459

VL - 18

SP - 31

EP - 41

JO - Pituitary

JF - Pituitary

SN - 1386-341X

IS - 1

ER -