2007 Fiscal Year Final Research Report Summary
Characterization of the epididymis-specific lipocalin promoters to develop male contraceptive drugs in future
| Project/Area Number |
18591792
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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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 | Tohoku University |
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Principal Investigator |
SUZUKI Kichiya Tohoku University, Tohoku University Hospital, Assistant Professor (30422116)
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| Co-Investigator(Kenkyū-buntansha) |
MURAKAMI Takashi Graduate School of Medicine, 大学院・医学系研究科, Associate Professor (20240666)
TERADA Yukihiro Tohoku University Hospital, 病院, Associate Professor (10260431)
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| Project Period (FY) |
2006 – 2007
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| Keywords | epididymis / gene regulation / androgen receptor / sperm maturation / male reproduction |
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| Research Abstract |
Sperm maturation process is one of the important function of the epididymis. If the process is specifically modulated, the sperm function for fertilizing ability may be disturbed. Therefore we hypothesized that characterization of epididymis-specific promoters would lead to the innovation of the male contraceptive drugs in future. As an initial study, we investigated the gene regulation mechanism of the Lipocalin 5 gene promoter. Lipocalin 5 is synthesized and secreted by the principal cells of the mouse middle/distal caput epididymidis and its regulation is androgen-dependent. We determined important cis-regulatory element between the 1.2 and 1.3 kb upstream region from transcription starting site using transgenic mice and epididymal cells. We also discovered that two androgen receptor binding sites and Foxal binding site exist in the 100 by fragment and that these molecules regulate gene expression of the Lipocalin 5 gene (Yu X, Suzuki K et al. Mol EndocrinoL 2007). Furthermore, we studied the Lipocalin 8 gene promoter as a second model, which is expressed in the initial segment and is regulated by transcription factors. We used same strategy as used for the Lipocalin 5 promoter study. Using transgenic mice, we established three lines carrying mutated Lipocalin 8 promoters ligated to the CAT reporter gene (3.0 kb, 1.7 kb, 0:3 kb). We confirmed that reporter gene expression level is decreased between 3.0 kb and 1.7 kb indicating that the 1.3-kb fragment contains important cis-regulatory element for the epididymis-specific gene expression, especially for the initial segment region.
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