{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T23:55:42Z","timestamp":1788306942176,"version":"build-2803163510"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"2","content-domain":{"domain":["eje.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2017,2]]},"abstract":"<jats:sec>\n<jats:title>Introduction<\/jats:title>\n<jats:p>In sporadic acromegaly, downregulation of AIP protein of the adenomas associates with invasive tumor features and reduced responsiveness to somatostatin analogues. AIP is a regulator of Ga<jats:sub>i<\/jats:sub> signaling, but it is not known how the biological function of the Ga<jats:sub>i<\/jats:sub> pathway is controlled.<\/jats:p><\/jats:sec>\n<jats:sec>\n<jats:title>Aim<\/jats:title>\n<jats:p>To study <jats:italic>GNAS<\/jats:italic> and <jats:italic>AIP<\/jats:italic> mutation status, AIP and Ga<jats:sub>i-2<\/jats:sub> protein expressions, Ki-67 proliferation indices and clinical parameters in patients having primary surgery because of acromegaly at a single center between years 2000 and 2010.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>Sixty patients (F\/M, 31\/29), mean age 49 (median 50), mean follow-up 7.7 years (range 0.6\u201314.0) underwent primary surgery. Four adenoma specimens (6.8%) harbored an <jats:italic>AIP<\/jats:italic> and 21 (35.6%) an activating <jats:italic>GNAS<\/jats:italic> (<jats:italic>Gsp<\/jats:italic>+) mutation. Altogether 13\/56 (23%) adenomas had low AIP protein levels, and 14\/56 (25%) low Ga<jats:sub>i-2<\/jats:sub> staining. In regression modeling, AIP expression associated with Ga<jats:sub>i-2<\/jats:sub> (<jats:italic>P<\/jats:italic>\u2009=\u20092.33\u2009\u00d7\u200910<jats:sup>\u22129<\/jats:sup>) and lower Ki-67 (<jats:italic>P<\/jats:italic>\u2009=\u20090.04). In pairwise comparison, low AIP protein predicted high GH at last follow-up (mean 7.7 years after surgery, <jats:italic>q<\/jats:italic>\u2009=\u20090.045). Extent of treatments given for acromegaly associated with higher preoperative GH (<jats:italic>P<\/jats:italic>\u2009=\u20097.94\u2009\u00d7\u200910<jats:sup>\u22124<\/jats:sup>), KNOSP (<jats:italic>P<\/jats:italic>\u2009=\u20090.003) and preoperative hypopituitarism (<jats:italic>P<\/jats:italic>\u2009=\u20090.03) and remission at last follow-up with change in 3-month postoperative IGF1 (<jats:italic>P<\/jats:italic>\u2009=\u20092.07\u2009\u00d7\u200910<jats:sup>\u22127<\/jats:sup>).<\/jats:p><\/jats:sec>\n<jats:sec>\n<jats:title>Conclusions<\/jats:title>\n<jats:p>We demonstrate, for the first time, that AIP protein expression associates with Ga<jats:sub>i-2<\/jats:sub> protein intensities in sporadic somatotropinomas, suggesting a joint regulation on somatostatin signaling. Low AIP level associates with higher proliferative activity and predicts high GH concentrations after long-term follow-up. The <jats:italic>AIP<\/jats:italic> mutation rate of 6.8% is fairly high, reflecting the genetic composition of the Finnish population.<\/jats:p>\n<\/jats:sec>","DOI":"10.1530\/eje-16-0620","type":"journal-article","created":{"date-parts":[[2016,12,21]],"date-time":"2016-12-21T01:35:24Z","timestamp":1482284124000},"page":"243-252","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":27,"title":["Impact of AIP and inhibitory G protein alpha 2 proteins on clinical features of sporadic GH-secreting pituitary adenomas"],"prefix":"10.1093","volume":"176","author":[{"given":"Elina","family":"Ritvonen","sequence":"first","affiliation":[{"name":"1EndocrinologyAbdominal Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esa","family":"Pitk\u00e4nen","sequence":"additional","affiliation":[{"name":"2Department of Medical and Clinical Genetics & Genome-Scale BiologyResearch Programs Unit, University of Helsinki, Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atte","family":"Karppinen","sequence":"additional","affiliation":[{"name":"3Department of NeurosurgeryUniversity of Helsinki and Helsinki University Hospital, Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satu","family":"Vehkavaara","sequence":"additional","affiliation":[{"name":"1EndocrinologyAbdominal Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hande","family":"Demir","sequence":"additional","affiliation":[{"name":"2Department of Medical and Clinical Genetics & Genome-Scale BiologyResearch Programs Unit, University of Helsinki, Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anders","family":"Paetau","sequence":"additional","affiliation":[{"name":"4Department of PathologyHUSLAB and University of Helsinki, Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camilla","family":"Schalin-J\u00e4ntti","sequence":"additional","affiliation":[{"name":"1EndocrinologyAbdominal Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Auli","family":"Karhu","sequence":"additional","affiliation":[{"name":"2Department of Medical and Clinical Genetics & Genome-Scale BiologyResearch Programs Unit, University of Helsinki, Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","reference":[{"key":"2016122017352905000_176.2.243.1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2006-1668"},{"key":"2016122017352905000_176.2.243.2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2012-4028"},{"key":"2016122017352905000_176.2.243.3","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2015-3129"},{"key":"2016122017352905000_176.2.243.4","doi-asserted-by":"publisher","DOI":"10.1038\/330566a0"},{"key":"2016122017352905000_176.2.243.5","doi-asserted-by":"publisher","DOI":"10.1210\/er.2012-1013"},{"key":"2016122017352905000_176.2.243.6","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1408028"},{"key":"2016122017352905000_176.2.243.7","doi-asserted-by":"publisher","DOI":"10.1126\/science.1126100"},{"key":"2016122017352905000_176.2.243.8","doi-asserted-by":"publisher","DOI":"10.1530\/ERC-13-0043"},{"key":"2016122017352905000_176.2.243.9","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2014.50"},{"key":"2016122017352905000_176.2.243.10","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(05)80056-X"},{"key":"2016122017352905000_176.2.243.11","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2002-021825"},{"key":"2016122017352905000_176.2.243.12","doi-asserted-by":"crossref","first-page":"E1411","DOI":"10.1210\/jc.2012-1111","article-title":"Somatostatin analogs modulate AIP in somatotroph adenomas: the role of the ZAC1 pathway","volume":"97","author":"Chahal","year":"2012","journal-title":"Journal Clinical Endocrinology and Metabolism"},{"key":"2016122017352905000_176.2.243.13","doi-asserted-by":"publisher","DOI":"10.1530\/ERC-12-0020"},{"key":"2016122017352905000_176.2.243.14","doi-asserted-by":"publisher","DOI":"10.1530\/ERC-12-0322"},{"key":"2016122017352905000_176.2.243.15","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-15-0832"},{"key":"2016122017352905000_176.2.243.16","doi-asserted-by":"publisher","DOI":"10.1016\/j.wneu.2015.02.024"},{"key":"2016122017352905000_176.2.243.17","doi-asserted-by":"publisher","DOI":"10.1111\/cen.12550"},{"key":"2016122017352905000_176.2.243.18","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1038\/nrendo.2014.21","article-title":"Expert consensus document: a consensus on the medical treatment of acromegaly","volume":"10","author":"Giustina","year":"2014","journal-title":"Nature Review Endocrinology"},{"key":"2016122017352905000_176.2.243.19","doi-asserted-by":"publisher","DOI":"10.1210\/jc.83.5.1624"},{"key":"2016122017352905000_176.2.243.20","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2007-2611"},{"key":"2016122017352905000_176.2.243.21","doi-asserted-by":"publisher","DOI":"10.1159\/000322787"},{"key":"2016122017352905000_176.2.243.22","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2009-2556"},{"key":"2016122017352905000_176.2.243.23","doi-asserted-by":"publisher","DOI":"10.1677\/ERC-09-0094"},{"key":"2016122017352905000_176.2.243.24","doi-asserted-by":"publisher","DOI":"10.1677\/JME-09-0009"},{"key":"2016122017352905000_176.2.243.25","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2010.02.012"},{"key":"2016122017352905000_176.2.243.26","doi-asserted-by":"publisher","DOI":"10.1210\/jcem-71-6-1421"},{"key":"2016122017352905000_176.2.243.27","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1227\/00006123-199308000-00003","article-title":"Clinical and biochemical characteristics of acromegalic patients harboring gsp-positive and gsp-negative pituitary tumors","volume":"33","author":"Adams","year":"1996","journal-title":"Neurosurgery"},{"key":"2016122017352905000_176.2.243.28","doi-asserted-by":"crossref","first-page":"R67","DOI":"10.1530\/JME-13-0172","article-title":"cAMP in the pituitary: an old messenger for multiple signals","volume":"52","author":"Peverelli","year":"2013","journal-title":"Journal of Molecular Endocrinology"},{"key":"2016122017352905000_176.2.243.29","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0700004104"},{"key":"2016122017352905000_176.2.243.30","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2006-2702"},{"key":"2016122017352905000_176.2.243.31","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-10-0327"},{"key":"2016122017352905000_176.2.243.32","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2011-2291"},{"key":"2016122017352905000_176.2.243.33","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2265.2008.03266.x"},{"key":"2016122017352905000_176.2.243.34","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/8.10.1913"}],"container-title":["European Journal of Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/eje.bioscientifica.com\/view\/journals\/eje\/176\/2\/243.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/eje.bioscientifica.com\/view\/journals\/eje\/176\/2\/243.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,14]],"date-time":"2023-02-14T16:34:37Z","timestamp":1676392477000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ejendo\/article\/176\/2\/243\/6655071"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,2]]},"references-count":34,"journal-issue":{"issue":"2"},"URL":"https:\/\/doi.org\/10.1530\/eje-16-0620","relation":{},"ISSN":["0804-4643","1479-683X"],"issn-type":[{"value":"0804-4643","type":"print"},{"value":"1479-683X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,2]]}}}