{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T03:13:32Z","timestamp":1787022812246,"version":"build-2736575974"},"reference-count":0,"publisher":"Oxford University Press (OUP)","issue":"1","content-domain":{"domain":["eje.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,7,1]]},"abstract":"\n Background<\/jats:title>\n \n POU1F1 encodes both PIT-1\u03b1, which plays pivotal roles in pituitary development and\n GH<\/jats:italic>\n , PRL and\n TSHB<\/jats:italic>\n expression, and the alternatively spliced isoform PIT-1\u03b2, which contains an insertion of 26-amino acids (\u03b2-domain) in the transactivation domain of PIT-1\u03b1 due to the use of an alternative splice acceptor at the end of the first intron. PIT-1\u03b2 is expressed at much lower levels than PIT-1\u03b1 and represses endogenous PIT-1\u03b1 transcriptional activity. Although\n POU1F1<\/jats:italic>\n mutations lead to combined pituitary hormone deficiency (CPHD), no patients with \u03b2-domain mutations have been reported.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Here, we report that a three-generation family exhibited different degrees of CPHD, including growth hormone deficiency with intrafamilial variability of prolactin\/TSH insufficiency and unexpected prolactinoma occurrence. The CPHD was due to a novel\n POU1F1<\/jats:italic>\n heterozygous variant (c.143-69T>G) in intron 1 of PIT-1\u03b1 (RefSeq number NM_000306) or as c.152T>G (p.Ile51Ser) in exon 2 of PIT-1\u03b2 (NM_001122757). Gene splicing experiments showed that this mutation yielded the PIT-1\u03b2 transcript without other transcripts. The lymphocyte PIT-1\u03b2 mRNA expression was significantly higher in the patients with the heterozygous mutation than a control. A luciferase reporter assay revealed that the PIT-1\u03b2-Ile51Ser mutant repressed PIT-1\u03b1 and abolished transactivation capacity for the rat prolactin promoter in GH3 pituitary cells.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n We describe, for the first time, that the PIT-1\u03b2 mutation can cause CPHD through a novel genetic mechanism, such as PIT-1\u03b2 overexpression, and that\n POU1F1<\/jats:italic>\n mutation might be associated with a prolactinoma. Analysis of new patients and long-term follow-up are needed to clarify the characteristics of PIT-1\u03b2 mutations.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1530\/eje-20-1313","type":"journal-article","created":{"date-parts":[[2021,4,22]],"date-time":"2021-04-22T13:31:33Z","timestamp":1619098293000},"page":"1-12","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-7","source":"Crossref","is-referenced-by-count":9,"title":["A mutation of the \u03b2-domain in POU1F1 causes pituitary deficiency due to dominant PIT-1\u03b2 expression"],"prefix":"10.1093","volume":"185","author":[{"given":"Shigeru","family":"Suzuki","sequence":"first","affiliation":[{"name":"1Department of Pediatrics, Asahikawa Medical University, Asahikawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kumihiro","family":"Matsuo","sequence":"additional","affiliation":[{"name":"1Department of Pediatrics, Asahikawa Medical University, Asahikawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiya","family":"Ito","sequence":"additional","affiliation":[{"name":"1Department of Pediatrics, Asahikawa Medical University, Asahikawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsushi","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"2Division of Metabolism and Biosystemic Science, Department of Medicine, Asahikawa Medical University, Asahikawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahide","family":"Kokumai","sequence":"additional","affiliation":[{"name":"1Department of Pediatrics, Asahikawa Medical University, Asahikawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akiko","family":"Furuya","sequence":"additional","affiliation":[{"name":"1Department of Pediatrics, Asahikawa Medical University, Asahikawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osamu","family":"Ueda","sequence":"additional","affiliation":[{"name":"1Department of Pediatrics, Asahikawa Medical University, Asahikawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tokuo","family":"Mukai","sequence":"additional","affiliation":[{"name":"1Department of Pediatrics, Asahikawa Medical University, Asahikawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koichi","family":"Yano","sequence":"additional","affiliation":[{"name":"1Department of Pediatrics, Asahikawa Medical University, Asahikawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenji","family":"Fujieda","sequence":"additional","affiliation":[{"name":"1Department of Pediatrics, Asahikawa Medical University, Asahikawa, Japan"},{"name":"3Department of Pediatrics, Asahikawa Medial University, Asahikawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akimasa","family":"Okuno","sequence":"additional","affiliation":[{"name":"1Department of Pediatrics, Asahikawa Medical University, Asahikawa, Japan"},{"name":"4Asahikawa Medical University, Asahikawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusuke","family":"Tanahashi","sequence":"additional","affiliation":[{"name":"1Department of Pediatrics, Asahikawa Medical University, Asahikawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Azuma","sequence":"additional","affiliation":[{"name":"1Department of Pediatrics, Asahikawa Medical University, Asahikawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","container-title":["European Journal of Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/eje.bioscientifica.com\/view\/journals\/eje\/185\/1\/EJE-20-1313.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/eje.bioscientifica.com\/downloadpdf\/journals\/eje\/185\/1\/EJE-20-1313.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,14]],"date-time":"2023-02-14T11:15:59Z","timestamp":1676373359000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ejendo\/article\/185\/1\/1\/6654390"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,1]]},"references-count":0,"journal-issue":{"issue":"1"},"URL":"https:\/\/doi.org\/10.1530\/eje-20-1313","relation":{},"ISSN":["0804-4643","1479-683X"],"issn-type":[{"value":"0804-4643","type":"print"},{"value":"1479-683X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,1]]}}}