2002 Fiscal Year Final Research Report Summary
THERAPUETIC APPLICATION OF AROMATASE INHIBITOR FOR LEIOMYOMA OF THE UTERUS AND ENDOMETRIOSIS
| Project/Area Number |
12557136
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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 | 展開研究 |
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| Research Field |
Obstetrics and gynecology
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| Research Institution | KANAAWA UNIVERSITY |
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Principal Investigator |
AHOZU Makio KANAAWA UNIVERSITY, University Hospital, Associate Professor (30226302)
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| Co-Investigator(Kenkyū-buntansha) |
INOUE Masaki 金沢大学, Graduate School, Professor (10127186)
KOIKE Kouji 金沢大学, Graduate School, Associate Professor (70225340)
SEGAWA Tomoya University Hospital, 医学部附属病院, Assistant Professor (40301197)
MURAKAMI KOUICHI University Hospital, 医学部附属病院, Assistant Professor (20242555)
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| Project Period (FY) |
2000 – 2002
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| Keywords | Aromatase / Endometriosis / Leromyoma of the uterus / Aromatase inhibitor / Estrogen / GnRH agonist / Clinical trial |
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| Research Abstract |
1. Leiomyoma of the uterus expresses estrogen synthetase (aromatase) and synthesize estrogen in situ. Preoperative GnRH agonist therapy abolishes aromatase expression in leiomyoma tissues in situ in addition to aromatase expression in the ovary. This combined suppression may explain why GnRH agonists induced shrinkage of leiomyoma more rapidly and more profoundly than natural menopause.
2. Addition of androstenedione stimulates cell proliferation of leiomyoma cells in culture. This growth stimulatory action was completely canceled by the pretreatment with an aromatase inhibitor (fadrozole).
3. Oral administration of fadrozole (1mg/kg/day,>1 weeks) induced anovulatory state in rats. Estrus cycles were recovered within 1 week after the discontinuation of fadrozole.
4. Oral fadrozole (2mg/day) induced rapid and profound regression of leiomyoma and resolved bulk-related symptoms of a perimenopausal woman. The potential uses of aromatase inhibitors was demonstrated.
5. AF-1/AD4BP binds to a nuclear half site of the most proximal promoter of aromatase (PII) and up-regulates the transcription of aromatase in endometriosis cells. Cis elements of PII promoter of aromatase, therefore its regulation, were quite different between endometriosis and the ovary, suggesting that tissues-specific and promoter-specific modulation of aromatase expression is possible.
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[Journal Article] Prepubertal gynecomastia due to estrogen excess associated with novel gain-of-function mutations affecting the aromatase gene.2003
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(in press)
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 gene.2003
Author(s)
Shozu, M., Sebastian, S., Takayama, K., Hsu, W.T., Schultz, R.A., Neely, K., Bryant, M., Bulun, S.E.
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Journal Title
N Engl J Med 348
Pages: 1855-1865
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Temporary amniotic membrane patching for acute chemical bums.2003
Author(s)
Kobayashi, A., Shirao, Y., Yoshita, T., Yagami, K., Segawa, Y., Kawasaki, K., Shozu, M., Tseng, S.C.
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Journal Title
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 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(和文)」より
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[Journal Article] Over-expression of aromatase P450 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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[Journal Article] Spatially heterogeneous expression of aromatase P450 through promoter II is closely correlated with the level of steroidogenic factor-1 transcript in endometrioma tissues.2002
Author(s)
Yang, H.J., Shozu, M., Murakami, K., Sumitani, H., Segawa, T., Kasai, T., Inoue, M.
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Journal Title
J Clin Endocrinol Metab 87
Pages: 3745-3753
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Regulation of aromatase activity in bone-derived cells : possible role of mitogen-activated protein kinase.2001
Author(s)
Shozu, M., Sumitani, H., Murakami, K., Segawa, T., Yang, H.J., Inoue, M.
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Journal Title
J Steroid Biochem Mol Biol 79
Pages: 61-65
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Regulation of aromatase activity in bone-derived cells : nossible2001
Author(s)
Shozu, M., Sumitani, H., Murakami, K., Segawa, T., Yang, H.J., Inoue, M.
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Journal Title
J Steroid Biochem Mol Biol 79
Pages: 61-65
Description
「研究成果報告書概要(欧文)」より
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