| Project/Area Number |
14370020
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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 | 一般 |
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| Research Field |
Environmental physiology (including Physical medicine and Nutritional physiology)
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| Research Institution | Gunma University |
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Principal Investigator |
KOIBUCHI Noriyuki Gunma University, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (80234681)
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| Co-Investigator(Kenkyū-buntansha) |
SHIMOKAWA Noriaki Gunma University, Graduate School of Medicine, Assistant Professor, 大学院・医学系研究科, 助教授 (90235680)
IWASAKI Toshiharu Gunma University, Graduate School of Medicine, Associate Professor, 大学院・医学系研究科, 講師 (80375576)
JINGU Hisaka Gunma University, Graduate School of Medicine, Assistant, 大学院・医学系研究科, 助手 (30292585)
TAKESHITA Akira Okinaka Memorial Institute for Medical Research, Invesitigator, 研究員 (20322646)
OKADA Junichi Gunma University, Graduate School of Medicine, Assistant Professor, 大学院・医学系研究科, 助教授 (80152304)
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| Project Period (FY) |
2002 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥13,800,000 (Direct Cost: ¥13,800,000)
Fiscal Year 2004: ¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 2003: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2002: ¥8,700,000 (Direct Cost: ¥8,700,000)
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| Keywords | Thyroid hormone / Cerebellum / Development / Critical Period / Gene expression / Transcriptional cofactor / Endocrine disrupters |
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| Research Abstract |
The aim of this study was to investigate the effect of thyroid hormone(TH) on brain development and the mechanisms generating the critical period of its action, using a rodent cerebellum as a model system.
Although the expression of TH receptor(TR) is greater in adult cerebellum, the sensitivity to TH is much less compared to that during cerebellar development. Thus, unknown factor other than TR may regulate its sensitivity. Thus, we investigated the ontogenic changes in the expression of SRC-1 that is a coactivator of TR to regulate transcription, by immunohistochemistry in the developing rat brain. SRC-1 was strongly expressed in the Purkinje cell. It was also weakly expressed in the internal granule cells. By Western blot, the level of SRC-1 protein was greatest at postnatal day (P) 14, the period when TH sensitivity is greatest.
Simultaneously, we have tried to clone the novel TR-binding protein in the fetal cerebellum, using Ras-Sos yeast two hybrid screening. We have identified a protein that has been known as OVCOV-1. The size of this protein is 365 amino acid in length. By sequence analysis, we found that three LXXLL motiefs that are responsible for binding to nuclear receptors.
Since previous studies have shown that perinatal exposure to several environmental chemical may induce abnormal brain development similar to those seen in hypothyroidism, we have examined the effect of polychlorinated biphenyls on TR-mediated transcription. Low dose (100 pM) PCB suppressed TR-mediated transcription. The effect of PCB was exerted by partial dissociation of TR from TH-responsive element of DNA.
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