Elucidation of a novel pathogenic mechanism for congenital hypopituitarism: functional analysis of a mutant PIT1B

Research Project

Project/Area Number	16H06608
Research Category	Grant-in-Aid for Research Activity Start-up
Allocation Type	Single-year Grants
Research Field	Pediatrics
Research Institution	Asahikawa Medical College
Principal Investigator	Suzuki Shigeru 旭川医科大学, 医学部, 助教 (80516394)
Project Period (FY)	2016-08-26 – 2018-03-31
Project Status	Completed (Fiscal Year 2017)
Budget Amount *help	¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000) Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000) Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords	下垂体機能低下症 / 遺伝 / 転写因子 / 遺伝子 / 小児内分泌学 / 先天性下垂体機能低下症
Outline of Final Research Achievements	A PIT1B mutation (PIT1B-T152G) identified in the patients with one dominant inherited family of combined hypopituitarism was investigated to elucidate a pathogenic mechanism. PIT1B-T152G suppressed the PIT1A mRNA expression, whose protein is essential for pituitary hormone production. Instead, PIT1B-T152G induced the own mRNA expression, which is unusual situation because PIT1B is much less expressed the normal condition. Heterologous expression studies of the mutated PIT1B-T152G protein showed modest reductions in its transactivation activities in HeLa cells, while acting as a dominant-negative inhibitor of the endogenous activities of PIT1A in pituitary GH3 cells. These data firstly showed that a PIT1B mutation causes congenital combined hypopituitarism.