{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T21:32:38Z","timestamp":1783632758036,"version":"3.55.0"},"reference-count":39,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2023,5,25]],"date-time":"2023-05-25T00:00:00Z","timestamp":1684972800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The glucose-dependent insulinotropic polypeptide receptor (GIPR) is aberrantly expressed in about one-third of GH-secreting pituitary adenomas (GH-PAs) and has been associated with a paradoxical increase of GH after a glucose load. The reason for such an overexpression has not yet been clarified. In this work, we aimed to evaluate whether locus-specific changes in DNA methylation patterns could contribute to this phenomenon. By cloning bisulfite-sequencing PCR, we compared the methylation pattern of the GIPR locus in GIPR-positive (GIPR+) and GIPR-negative (GIPR\u2212) GH-PAs. Then, to assess the correlation between Gipr expression and locus methylation, we induced global DNA methylation changes by treating the lactosomatotroph GH3 cells with 5-aza-2\u2032-deoxycytidine. Differences in methylation levels were observed between GIPR+ and GIPR\u2212 GH-PAs, both within the promoter (31.9% vs. 68.2%, p &lt; 0.05) and at two gene body regions (GB_1 20.7% vs. 9.1%; GB_2 51.2% vs. 65.8%, p &lt; 0.05). GH3 cells treated with 5-aza-2\u2032-deoxycytidine showed a ~75% reduction in Gipr steady-state level, possibly associated with the observed decrease in CpGs methylation. These results indicate that epigenetic regulation affects GIPR expression in GH-PAs, even though this possibly represents only a part of a much more complex regulatory mechanism.<\/jats:p>","DOI":"10.3390\/ijms24119264","type":"journal-article","created":{"date-parts":[[2023,5,26]],"date-time":"2023-05-26T02:05:44Z","timestamp":1685066744000},"page":"9264","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["The Methylation Analysis of the Glucose-Dependent Insulinotropic Polypeptide Receptor (GIPR) Locus in GH-Secreting Pituitary Adenomas"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9419-830X","authenticated-orcid":false,"given":"Mattia","family":"Dalle Nogare","sequence":"first","affiliation":[{"name":"Department of Biology, University of Padova, 35128 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"D\u2019Annunzio","sequence":"additional","affiliation":[{"name":"Department of Cellular, Computational and Integrative Biology (CIBIO), University of Trento, 38123 Trento, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Vazza","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Padova, 35128 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1942-7202","authenticated-orcid":false,"given":"Daniela","family":"Regazzo","sequence":"additional","affiliation":[{"name":"Endocrinology Unit, Department of Medicine, Padova University Hospital, 35121 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luna","family":"Picello","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Padova, 35128 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2529-6149","authenticated-orcid":false,"given":"Luca","family":"Denaro","sequence":"additional","affiliation":[{"name":"Academic Neurosurgery, Department of Neurosciences, Padova University Hospital, 35121 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giacomo","family":"Voltan","sequence":"additional","affiliation":[{"name":"Endocrinology Unit, Department of Medicine, Padova University Hospital, 35121 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla","family":"Scaroni","sequence":"additional","affiliation":[{"name":"Endocrinology Unit, Department of Medicine, Padova University Hospital, 35121 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1456-8716","authenticated-orcid":false,"given":"Filippo","family":"Ceccato","sequence":"additional","affiliation":[{"name":"Endocrinology Unit, Department of Medicine, Padova University Hospital, 35121 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4065-4677","authenticated-orcid":false,"given":"Gianluca","family":"Occhi","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Padova, 35128 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"103","DOI":"10.2174\/138945012798868434","article-title":"The Family B1 GPCR: Structural Aspects and Interaction with Accessory Proteins","volume":"13","author":"Couvineau","year":"2011","journal-title":"Curr. 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