| 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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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥11,800,000 (Direct Cost: ¥11,800,000)
Fiscal Year 2002: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2001: ¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 2000: ¥5,100,000 (Direct Cost: ¥5,100,000)
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| Keywords | Aromatase / Endometriosis / Leromyoma of the uterus / Aromatase inhibitor / Estrogen / GnRH agonist / Clinical trial / アロマターゼ阻害例 / アロマターゼインヒビター / GnRH アゴニスト |
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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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