{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T04:49:35Z","timestamp":1790743775891,"version":"4.1.0"},"reference-count":88,"publisher":"The Endocrine Society","issue":"12","license":[{"start":{"date-parts":[[2021,8,21]],"date-time":"2021-08-21T00:00:00Z","timestamp":1629504000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000071","name":"National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["R00HD087430"],"award-info":[{"award-number":["R00HD087430"]}],"id":[{"id":"10.13039\/100000071","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Pituitary adenomas have a staggering 16.7% lifetime prevalence and can be devastating in many patients because of profound endocrine and neurologic dysfunction. To date, no clear genomic or epigenomic markers correlate with their onset or severity. Herein, we investigate the impact of the O-GlcNAc posttranslational modification in their etiology. Found in more than 7000 human proteins to date, O-GlcNAcylation dynamically regulates proteins in critical signaling pathways, and its deregulation is involved in cancer progression and endocrine diseases such as diabetes. In this study, we demonstrated that O-GlcNAc enzymes were upregulated, particularly in aggressive adrenocorticotropin (ACTH)-secreting tumors, suggesting a role for O-GlcNAcylation in pituitary adenoma etiology. In addition to the demonstration that O-GlcNAcylation was essential for their proliferation, we showed that the endocrine function of pituitary adenoma is also dependent on O-GlcNAcylation. In corticotropic tumors, hypersecretion of the proopiomelanocortin (POMC)-derived hormone ACTH leads to Cushing disease, materialized by severe endocrine disruption and increased mortality. We demonstrated that Pomc messenger RNA is stabilized in an O-GlcNAc-dependent manner in response to corticotrophin-releasing hormone (CRH). By affecting Pomc mRNA splicing and stability, O-GlcNAcylation contributes to this new mechanism of fast hormonal response in corticotropes. Thus, this study stresses the essential role of O-GlcNAcylation in ACTH-secreting adenomas\u2019 pathophysiology, including cellular proliferation and hypersecretion.<\/jats:p>","DOI":"10.1210\/endocr\/bqab178","type":"journal-article","created":{"date-parts":[[2021,8,21]],"date-time":"2021-08-21T13:24:25Z","timestamp":1629552265000},"source":"Crossref","is-referenced-by-count":8,"title":["<i>O<\/i>\n                    -GlcNAcylation Is Essential for Rapid\n                    <i>Pomc<\/i>\n                    Expression and Cell Proliferation in Corticotropic Tumor Cells"],"prefix":"10.1210","volume":"162","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5579-4798","authenticated-orcid":false,"given":"Logan J","family":"Massman","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Medical College of Wisconsin, Milwaukee, Wisconsin, 53226, USA"},{"name":"Department of Neurosurgery, Medical College of Wisconsin, Milwaukee, Wisconsin, 53226, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7287-5450","authenticated-orcid":false,"given":"Michael","family":"Pereckas","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Medical College of Wisconsin, Milwaukee, Wisconsin, 53226, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9795-9303","authenticated-orcid":false,"given":"Nathan T","family":"Zwagerman","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Medical College of Wisconsin, Milwaukee, Wisconsin, 53226, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2033-5241","authenticated-orcid":false,"given":"Stephanie","family":"Olivier-Van Stichelen","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Medical College of Wisconsin, Milwaukee, Wisconsin, 53226, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2021,8,21]]},"reference":[{"issue":"3","key":"2021121717260292600_CIT0001","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1002\/cncr.20412","article-title":"The prevalence of pituitary adenomas: a systematic review","volume":"101","author":"Ezzat","year":"2004","journal-title":"Cancer."},{"key":"2021121717260292600_CIT0002","doi-asserted-by":"crossref","first-page":"v1","DOI":"10.1093\/neuonc\/nos218","article-title":"CBTRUS statistical report: Primary brain and central nervous system tumors diagnosed in the United States in 2005-2009","volume":"14","author":"Dolecek","year":"2012","journal-title":"Neuro-Oncol."},{"issue":"3","key":"2021121717260292600_CIT0003","doi-asserted-by":"crossref","first-page":"527","DOI":"10.3171\/2014.5.JNS131819","article-title":"Descriptive epidemiology of pituitary tumors in the United States, 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