2017 Fiscal Year Final Research Report
Elucidation of a novel pathogenic mechanism for congenital hypopituitarism: functional analysis of a mutant PIT1B
| Project/Area Number |
16H06608
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Single-year Grants |
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| Research Field |
Pediatrics
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| Research Institution | Asahikawa Medical College |
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Principal Investigator |
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| Project Period (FY) |
2016-08-26 – 2018-03-31
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| Keywords | 下垂体機能低下症 / 遺伝 / 転写因子 |
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| 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.
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| Free Research Field |
小児内分泌学
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