2003 Fiscal Year Final Research Report Summary
Steroidogenic factor-1 as a therapeutic target for of severe ovarian failure
| Project/Area Number |
13470348
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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 |
Obstetrics and gynecology
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| Research Institution | Kanazawa University |
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Principal Investigator |
SHOZU Makio Kanazawa University, Hospital, Center for perinatal and reproductive health, associate professor, 医学部附属病院, 助教授 (30226302)
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| Co-Investigator(Kenkyū-buntansha) |
INOUE Masaki Kanazawa University, Graduate School of Obstetrics and Gynecology, professor, 医学系研究科, 教授 (10127186)
MURAKAMI Koichi Kanazawa University, Hospital, Center for perinatal and reproductive health, assistant professor, 医学部附属病院, 助手 (20242555)
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| Project Period (FY) |
2001 – 2003
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| Keywords | aromatase / granulosa cells / steroidogenic factor-1 / IL-β / estrogen / ovulation |
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| Research Abstract |
Aromatization of androgens, catalyzed by aromatase P450, is essential for estrogen biosynthesis, hetero for folliculogenesis. Here we investigated the transcriptional regulation of aromatase in granulosa cells and identify both steroidogenic factor-1 and LRH-1 as important regulatory factors binding to the nuclear half site of proximal promoter PII of aromatase. Both transcriptional factors were expressed in granulosa cell of healthy growing follicles and luteal cells. COV432, a cell lines established from a human granulosa cell, express exclusively LRH-1 and granulosa cells in growing follicle expressed much LRH-1 than SF-l. Granulosa luteal cells expressed much LRH-1, while theca luteal cells almost exclusively expressed SF-1. Co-expression of SF-1 or LRH-1 stimulated the expression of promoter vectors containing various lengths of PII sequences. We also investigated mechanism of IL-lb- and GnRH agonsit- induced induction of aromatase in endometriosis-derived stromal cells. IL-lb increased aromatase expression through COX2-dependent and COX2-independent mechanisms. GnRH agonists transiently stimulated aromatase expression through the activation of PKC. IGF-1 and BMP also stimulated aromatase expression in the presence of FSH.
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Research Products
(27 results)
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[Journal Article] Estrogen excess associated with novel gain-of-function mutations affecting the aromatase gene2003
Author(s)
Shozu, M., Sbastian, S., Takayama, K., Hsu, W.-T., Schultz, M., Neely, K., Bryant, M., Bulun, S.E.
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Journal Title
New Engl J Med 348・19
Pages: 1855-1865
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Estrogen excess associated with novel gain-of-function mutations affecting the aromatase gene2003
Author(s)
Shozu, M., Sbastian, S., Takayama, K., Hsu, W.-T., Schultz, M., Neely, K., Bryant, M., Bulun, S.E.
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Journal Title
New Engl J-Med 348・19
Pages: 1855-65
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Over-expression of aromatase P-450 in leiomyoma tissues in driven through the promoter I.4 of aromatase P-450.2002
Author(s)
Shozu, M., Sumitani, H., Segawa, T., Yang, H.-J., Murakami, K., Kasai, T., Inoue, M.
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Journal Title
J Clin Endocrinol Metab 87
Pages: 2540-2548
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Over-expression of aromatase P-450 in leiomyoma tissues is driven through the promoter 1.4 of aromatase P-450.2002
Author(s)
Shozu, M., Sumitani, H., Segawa, T., Yang, H.-J., Murakami, K., Kasai, T., Inoue, M.
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Journal Title
J Clin Endocrinol Metab 87
Pages: 2540-2548
Description
「研究成果報告書概要(欧文)」より
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