Faculty Collaboration Database

The diverging role of O-GlcNAc transferase in corticotroph and somatotroph adenomas. Pituitary 2024 Oct;27(5):577-589

Date

07/28/2024

Pubmed ID

39066842

Pubmed Central ID

PMC12147819

DOI

10.1007/s11102-024-01431-x

Scopus ID

2-s2.0-85200049784 (requires institutional sign-in at Scopus site)   1 Citation

Abstract

PURPOSE: Molecular mechanisms involved in the pathogenesis and tumor progression of pituitary adenomas (PA) remain incompletely understood. Corticotroph and somatotroph PA are associated with a high clinical burden, and despite improved surgical outcomes and medical treatment options, they sometimes require multiple surgeries and radiation. Preliminary data suggested a role for O-GlcNAc Transferase (OGT), the enzyme responsible for the O-GlcNAcylation of proteins. O-GlcNAcylation and OGT have been found elevated in other types of tumors.

METHODS: We evaluated 60 functioning and nonfunctioning PA (NFPA) from operated patients and postmortem normal and tumoral pituitary tissue by immunohistochemistry. We performed transcriptomic analyses to explore the relevance of the O-GlcNAc Transferase (OGT) in PAs. We detected OGT in immunobiological analysis and define its level in PA tissue in patients.

RESULTS: OGT was strongly associated with PA hormone secretory capacity in functioning PA and with tumor growth in NFPAs. In NFPAs, OGT was positively associated with tumor size but not with cavernous sinus invasion (Knosp grading). In GH-secreting PA, OGT expression was negatively correlated with circulating Insulin-like Growth Factor 1 level. In adrenocorticotropic hormone (ACTH)-secreting PA, OGT expression was positively associated with circulating ACTH levels. OGT did not correlate with tumor size in secreting PAs. OGT levels were higher in gonadotroph PA compared to normal glands.

CONCLUSION: O-GlcNAcylation can be downregulated in non-cancerous tumors such as GH-secreting adenomas. Future studies are warranted to elucidate the role of OGT in the pathogenesis of PAs.

Author List

Gonzalez R, Massman L, Ho S, Luna S, Cheok S, Liang B, Mrachek K, Coss D, Ioachimescu AG, Zwagerman N, Olivier-Van Stichelen S

Authors

Stephanie K. Cheok MD Assistant Professor in the Neurosurgery department at Medical College of Wisconsin
Adriana G. Ioachimescu MD, PhD Professor in the Medicine department at Medical College of Wisconsin
Edward Kelly S. Mrachek MD Assistant Professor in the Pathology department at Medical College of Wisconsin
Stephanie Olivier-Van Stichelen PhD Associate Professor in the Biochemistry department at Medical College of Wisconsin
Nathan Zwagerman MD Associate Professor in the Neurosurgery department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

ACTH-Secreting Pituitary Adenoma
Adenoma
Adult
Aged
Corticotrophs
Female
Growth Hormone-Secreting Pituitary Adenoma
Humans
Male
Middle Aged
N-Acetylglucosaminyltransferases
Pituitary Neoplasms