| Project/Area Number |
14580650
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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 |
Functional biochemistry
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| Research Institution | Kyushu University |
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Principal Investigator |
OGISHIMA Tadashi (2003) Kyushu University, Faculty of Sciences, Assoc.Prof., 理学研究院, 助教授 (70177153)
伊藤 明夫 (2002) 九州大学, 理学研究院, 教授 (30037379)
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| Co-Investigator(Kenkyū-buntansha) |
荻島 正 九州大学, 理学研究院, 助教授 (70177153)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2003: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2002: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | Outer mitochondrial membrane cytochrome b / cytochrome b_5 / cytochrome P-45O_<17α> / Membrane Transport / Androgengenesis / Thetis / Purkinje cells / choroid plexus / 外膜シトクロムb5 / ミトコンドリア外膜 / 小胞体 / 細胞内輸送 / デキサメサゾン |
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| Research Abstract |
Outer mitochondrial membrane cytochrome b (OMb) was discovered in rat liver as a homologue of microsomal cytochrome b_5 (b_5). OMb was co-localized in Leydig cells with cytochrome P-450_<17α>, which catalyzes androgengenesis therein, whereas b_5 was undetectable. We have demonstrated that OMb stimulates the 17α-hydroxylase and lyase reactions of P-45O_<17α> under limited but physiological amounts of P-450 reductase, leading to an enhanced production of androstenedione from progesterone. Thus, OMband not b_5, which was believed to be responsible for the activation, was identified as a modulator for androgengenesis in rat testes. This finding prompted us to study the novel physiological functions of OMb. We analyzed the tissue localization of OMb, b_5 and P-45O_<17α> in rats by immunohistochemical staining. In the adrenal cortex OMb and b_5 were mainly present in the outer and inner portions, respectively. In the cerebellum OMb and P-450_<17α> were only detected and co-localized in the Purkinje cell, a major site for neurosteroidogenesis. In cerebrum they were co-localized in the ependymal cells of choroid plexus, which produces the cerebrospinal fluid. OMb was present also in the hippocampus and ganglionic layer. In contrast, b_5 was scarcely observed in the brain. Partially purified Purkinje cells produced testosterone from progesterone, indicating that both P-450_<17α> and 17β-hydroxysteroid dehydrogenase were active in the conversion and suggested that OMb could be responsible for stimulation of P-450_<17α>-catalyzed reactions in the cells. These results imply important functions of OMb in not only ordinary endocrine systems but also in higher life activities.
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