Expression of the pituitary stem/progenitor marker GFR?2 in human pituitary adenomas and normal pituitary.

ABSTRACT: 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 (GFR?2), a recently described pituitary stem/progenitor marker, might be differentially expressed in pituitary adenomas versus normal pituitary.The expression of GFR?2 and other members of the GFR receptor family (GFR?1, ?3, ?4) 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.GFR?2 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, GFR?2 was significantly over-expressed (~5-fold) in the gonadotropinoma subtype only (p < 0.05). GFR?2 protein expression appeared to be higher in most NFAs, although there was heterogeneity in protein expression in this group. GFR?2 protein expression appeared consistently lower in functioning adenomas by IHC and western blot. In normal pituitary, GFR?2 was localized in Rathke's remnant, the putative pituitary stem cell niche, and in corticotropes.Our results suggest that the pituitary stem cell marker GFR?2 is under-expressed in functioning adenomas and over-expressed in NFAs, specifically gonadotropinomas. Further studies are required to elucidate whether over-expression of GFR?2 in gonadotropinomas might play a role in pituitary tumorigenesis.

SUBMITTER: Mathioudakis N 

PROVIDER: S-EPMC4090297 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature