| Project/Area Number |
16209049
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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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 | Chiba University (2005-2007)
Kanazawa University (2004) |
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Principal Investigator |
SHOZU Makio Chiba University, Department of Reproductive Medicine, Professor (30226302)
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| Co-Investigator(Kenkyū-buntansha) |
INOUE Masaki Kanazawa University, Graduate School of Medical Science, Department of Obstetrics and Gynecology, Professor (10127186)
MITSUHASHI Akira Graduate School of Medicine, Chiba University, Department of Reproductive Medicine, Lecture (40302541)
USUI Hirokazu Graduate School of Medicine, Chiba University, Department of Reproductive Medicine, Associate Professor (90375634)
KIHARA Maki Chiba University Hospital, Department of Gynecology, Assistant Professor (20375760)
MURAKAMI Koichi Kanazawa University, Graduate School of Medical Science, Department of Obstetrics and Gynecology, Associate Professor (20242555)
小野 俊介 金沢大学, 自然科学系研究科, 助教授 (40345591)
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| Project Period (FY) |
2004 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥38,740,000 (Direct Cost: ¥29,800,000、Indirect Cost: ¥8,940,000)
Fiscal Year 2007: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2006: ¥7,930,000 (Direct Cost: ¥6,100,000、Indirect Cost: ¥1,830,000)
Fiscal Year 2005: ¥11,960,000 (Direct Cost: ¥9,200,000、Indirect Cost: ¥2,760,000)
Fiscal Year 2004: ¥12,350,000 (Direct Cost: ¥9,500,000、Indirect Cost: ¥2,850,000)
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| Keywords | aromatase / inhibitor / uterine leiomyoma / endometriosis / ovulation induction / 催奇形性 / 排卵障害 / 妊孕性 / 脂肪 |
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| Research Abstract |
Estrogen-dependent gynecologic diseases such as endometriosis, uterine leiomyoma and adenomyosis has been increased and worsened with a recent trend to late- or un-marriage in life. The older women become, the more difficult she ovulate. We have shown that an aromatase inhibitor(s) is a theoretical molecular target of endocrine therapy of these estrogen-dependent diseases as well as a specific ovulatory failure (PCOS). Here we examined therapeutic mechanisms of an aromatase inhibitor and showed the possible clinical usefulness of an aromatase inhibitor for management of the situations described earlier. In leiomyoma cells, enhanced expression of aromatase increased in situ estrogen, which possibly promoted the proliferation of their own. Absent activation of MAPK pathway in leiomyoma cells also contributed to enhanced cell proliferation through the reduction in Egr-1, resulting in low Rb expression. IGF-1 enhanced accumulation of aromatase in leiomyoma cells by deprivation of trafficking newly synthesized aromatase into lysosome, probably mediated by IGF-1 action on mTOR. There was a racial difference in aromatase expression of leiomyoma cells. It was shown that local application of a drug delivery system composed of fadrozole- or danazole-loaded hyaluronic acid successfully treated rat chocolate cyst model without systemic effect. Fadrozole was preoperatively administered to leiomyoma patients, who gave their consent for the study. Two third of patients showed reduction in volume by 25% with an improvement of symptoms, within the first 4 weeks. Another inhibitor of aromatase, letrozole, was administered to PCOS patients with an informed consent and found the letrozole was as effective as clomiphene in terms of ovulation induction and might be more beneficial to patients with implantation difficulty compared to clomiphene.
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