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

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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.

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Acknowledgments

The authors wish to acknowledge Mr. Moses Chappell in the Department of Pathology for his assistance in obtaining pituitary autopsy specimens, and Ms. Leslie Reynolds in the Department of Pathology for her assistance in obtaining pituitary tumor slides. This work was supported by NIH T32 Grant #5T32DK007751-15 (NM) and NIH R01 NS070024 (AQH).

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Authors and Affiliations

  1. Division of Endocrinology, Diabetes, and Metabolism, Johns Hopkins University School of Medicine, 1830 E. Monument Street, Suite 333, Baltimore, MD, 21287, USA

    Nestoras Mathioudakis & Roberto Salvatori

  2. Department of Neurological Surgery, Johns Hopkins University School of Medicine, 4940 Eastern Ave, 301 Mason Lord Drive, Suite 2100, Baltimore, MD, 21224, USA

    Ram Sundaresh, Alexandra Larsen, William Ruff, Jennifer Schiller, Hugo Guerrero-Cázares & Alfredo Quiñones-Hinojosa

  3. Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Peter Burger

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  1. Nestoras Mathioudakis
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Correspondence to Nestoras Mathioudakis.

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Mathioudakis, N., Sundaresh, R., Larsen, A. et al. Expression of the pituitary stem/progenitor marker GFRα2 in human pituitary adenomas and normal pituitary. Pituitary 18, 31–41 (2015). https://doi.org/10.1007/s11102-014-0553-1

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