2010 Fiscal Year Final Research Report
Molecular mechanism leading to impaired sexual differentiation and reproductive failure in patients with MAMLD mutations
| Project/Area Number |
20390265
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Endocrinology
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| Research Institution | National Research Institute for Child Health and Development |
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Principal Investigator |
FUKAMI Maki National Research Institute for Child Health and Development, 臨床内分泌研究室, 室長 (40265872)
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| Co-Investigator(Kenkyū-buntansha) |
WADA Yuka 独立行政法人 国立成育医療研究センター, 分子内分泌研究部, 研究員 (80399485)
OGATA Tsutomu 独立行政法人 国立成育医療研究センター, 分子内分泌研究部, 部長 (40169173)
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| Project Period (FY) |
2008 – 2010
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| Keywords | 生殖内分泌学 / 性分化 / 性ホルモン / ステロイド / MAMLD1 |
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| Research Abstract |
Clinical analysis of mutation-positive patients indicated that loss of function of MAMLD1 leads to various clinical features including abnormal genitalia, testosterone deficiency, impaired spermatogenesis and infertility. In vitro assays suggested that Mamld1 enhances Cyp17a1 expression primarily in Leydig cells and permit to produce a sufficient amount of testosterone for male sex development. Collectively, it is likely that SF1-MAMLD1-CYP17A1 axis plays a critical role in regulation of testosterone production in the testis.
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[Journal Article] Cytochrome P450 Oxidoreductase Deficiency : Identification and Characterization of Biallelic Mutations and Genotype-Phenotype Correlations in 35 Japanese Patients.2009
Author(s)
Fukami M, Nishimura G, Homma K, Nagai T, Hanaki K, Uematsu A, Ishii T, Numakura C, Sawada H, Nakacho M, Kowase T, Motomura K, Haruna H, Nakamura M, Ohishi A, Adachi M, Tajima T, Hasegawa Y, Hasegawa T, Horikawa R, Fujieda K, Ogata T.
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Journal Title
J Clin Endocrinol Metab. 94(5)
Pages: 1723-1731
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[Journal Article] Mastermind-like domain-containing 1 (MAMLD1 or CXorf6) transactivates the Hes3 promoter, augments testosterone production, and contains the SF1 target sequence.2008
Author(s)
Fukami M, Wada Y, Okada M, Kato F, Katsumata N, Baba T, Morohashi K, Laporte J, Kitagawa M, Ogata T.
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Journal Title
J Biol Chem. 283(9)
Pages: 5525-5532
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[Journal Article] Aromatase Excess Syndrome : Identification of Cryptic Duplications and Deletions Leading to Gain-of-Function of CYP19A1 and Assessment of Phenotypic Determinants.
Author(s)
Fukami M, Shozu M, Soneda S, Kato F, Inagaki A, Takagi H, Hanaki K, Kanzaki S, Ohyama K, Sano T, Nishigaki T, Yokoya S, Binder G, Horikawa R, Ogata T
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Journal Title
J Clin Endocrinol Metab. in press
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[Presentation] A gain of function mutation in the MAMLD1 discloses a new pathway in the etiology of 46, XY disorders of sex development.2009
Author(s)
Brandao MP, Fukami M, Mendonca BB, Santos MG, Domenice S, Arnold IJP, Ogata T, Costa EMF.
Organizer
The 8th Joint meeting, ESPE-LWPES in association with APEG, APPES, SLEP, JSPE.
Place of Presentation
New York,
Year and Date
20090909-20090912
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