| Project/Area Number |
09557131
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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 | Osaka University |
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Principal Investigator |
KURACHI Hirohisa Medical School, Osaka University, Associate professor, 医学系研究科, 助教授 (40153366)
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| Co-Investigator(Kenkyū-buntansha) |
MORISHIGE Kenichiro Medical School, Osaka University, Assistant, 医学系研究科, 助手 (90283788)
田坂 慶一 大阪大学, 医学部, 講師 (50155058)
山本 敏也 大阪大学, 医学部, 助手 (80283787)
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| Project Period (FY) |
1997 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥12,300,000 (Direct Cost: ¥12,300,000)
Fiscal Year 1999: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1998: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1997: ¥8,300,000 (Direct Cost: ¥8,300,000)
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| Keywords | estrogen / obesity / lipid metabolism / adipocyte / lipoprotein lipase / estrogen receptor / transcription factor / transcriptional regulation / 転写制御 / 変異遺伝子 / 閉経 |
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| Research Abstract |
Estrogen exerts a variety of effects not only on female reproductive organs but also on nonreproductive organs, including adipose tissue. Estrogen inhibits obesity trggered by ovariectomy in rodents. We studied the mechanism underlying this estrogen-dependent inhibition of obesity. Estrogen markedly decreased the amounts of fat accumulation and lipoprotein lipase (LPL) mRNA as well as triglyceride accumulation in genetically manipulated 3T3-L1 adipocytes stably expressing the estrogen receptor (ER). Transcriptional regulation of the murine LPL gene by estrogen was then studied. A pLPL (1980)-CAT construct, along with an ER expression vector, was introduced into differentated 3T3-L1 cells. and CAT activities were determined. ER, mostly ligand-dependently, inhibited the basal LPL promoter activity by 7-fold. We searched the LPL promoter for an estrogen-responsive suppressive element by employing a set of 5'-deletion mutants of the pLPL-CAT reporter. Although there was no classical estrogen response element, it was demonstrated that an AP-1-like TGGAATTC sequence located at (-1856/-1850) was responsible for the suppression of the LPL gene transcription by estrogen. An electrophoretic mobility shift assay probed with the TGAATTC sequence demonstrated formation of a specific DNA-nuclear protein complex. Interestingly, this complex was not affected by the addition of any antibodies against ER, c-Jun, c-Fos, JunB, or JunD. These results may indicate the existence of a unique signaling pathway utilizing a unique estrogen response element other than classical ERE and binding proteins which possibly regulate transcription of the LPL gene.
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