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

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 (GFR alpha 2), a recently described pituitary stem/progenitor marker, might be differentially expressed in pituitary adenomas versus normal pituitary. Methods The expression of GFR alpha 2 and other members of the GFR receptor family (GFR alpha 1, alpha 3, alpha 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. Results GFR alpha 2 mRNA was similar to 2.6 fold under-expressed in functioning adenomas (p<0.01) and similar to 3.5 fold over-expressed in non-functioning adenomas (NFAs) (p<0.05) compared to normal pituitary. Among NFAs, GFR alpha 2 was significantly over-expressed (similar to 5-fold) in the gonadotropinoma subtype only (p<0.05). GFR alpha 2 protein expression appeared to be higher in most NFAs, although there was heterogeneity in protein expression in this group. GFR alpha 2 protein expression appeared consistently lower in functioning adenomas by IHC and western blot. In normal pituitary, GFR alpha 2 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 GFR alpha 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 alpha 2 in gonadotropinomas might play a role in pituitary tumorigenesis.