1997 Fiscal Year Annual Research Report

脳内ニューロステロイドの生合成制御機構と作用機構に関する研究

Research Project

Project/Area Number	08454265
Research Institution	HIROSHIMA UNIVERSITY
Principal Investigator	筒井和義広島大学, 総合科学部, 教授 (20163842)
Co-Investigator(Kenkyū-buntansha)	古川康雄広島大学, 理学部, 助教授 (40209169) 山崎岳広島大学, 総合科学部, 助手 (30192397) 小南思郎広島大学, 総合科学部, 教授 (10106776)
Keywords	脊椎動物 / 脳 / プルキンエ細胞 / ニューロステロイド / プロジェステロン / プレグネノロン硫酸エステル / 3β-HSD / 学習と記憶
Research Abstract	脳内ニューロステロイド合成酵素の遺伝子発現を哺乳類や鳥類を材料に分子生物学的手法により解析したところ、コレステロールからプレグネノロンを合成するシトクロームP450sccの遺伝子は大脳、間脳、中脳、小脳において広く発現することがわかった。一方、プレグネノロンをもとにプロジェステロンを合成する3β-HSD(3β-水酸基脱水素酵素)は小脳と大脳において、プレグネノロンからデヒドロエピアンドロステロンを合成するシトクロームP45017α、リアーゼは中脳においてのみ発現するこが明らかになった。これらの酵素が発現する細胞を同定したところ、P450sccと3β-HSDの顕著な遺伝子発現は小脳皮質ニューロンのプルキンエ細胞において認められた。このニューロンでは、P450sccは生後から成熟期にかけて常に発現しており、プレグネノロンとその硫酸エステルが合成されることがわかった。さらに、新生期のプルキンエ細胞においてはP450sccに加え3β-HSDも発現し、この時期に限りプロジェステロンも合成されることが見いだされた。プルキンエ細胞を実験モデルにして、この細胞が合成するニューロステロイドの作用を電気生理学的に解析したところ、プレグネノロン硫酸エステルはGABAの放出によるプルキンエ細胞への情報伝達を変化させることが見いだされた。一方、新生期にはプロジェステロンは小脳皮質においてプルキンエ細胞の発達と神経回路の構築を促進していることが示唆された。プルキンエ細胞は記憶ニューロンとして知られ、現在ニューロステロイドが学習・記憶に関わる脳内分子であることを証明するために、行動実験を進めている。

Research Products
(30 results)

All Other

All Publications (30 results)

[Publications] Y.Azumaya: "Existence and localization of a splicing factor U2AF-like protein in the zebra finch brain." J.Exp.Zool.280(in press). (1998)
[Publications] T.Yamazaki: "Kinetic analysis of successive reaction catalyzed by bovine cytochrome p450_<17α,lyase>." Biochemistry. (in press). (1998)
[Publications] K.Ukena: "Cytochrome P450 side-cain cleavage enzyme (P450scc) in the cerebellar Purkinje neuron and its neonatal change in rats." Endocrinology. 139. 137-147 (1998)
[Publications] T.Niida: "Characterization of binding of the annelidan myoactive peptides,GGNG peptides,to tissues of the earthworm,Eisenia foetida." J.Exp.Zool.279. 562-570 (1997)
[Publications] M.Takase: "Inhibition of prolactin in the downregulation of testicular follicle-stimulating hormone receptors in mice." J.Exp.Zool.278. 234-242 (1997)
[Publications] T.Kotegawa: "Inhibitory role of opioid peptides in the regulation of aggressive and sexual behaviors in male Japanese quails." J.Exp.Zool.277. 146-154 (1997)
[Publications] K.Tsutsui: "Demonstration,localization,and development of galanin receptors in the quail oviduct." J.Exp.Zool.277. 57-65 (1997)
[Publications] K.Ukena: "Immunochemical demonstration of Eisenia tetradecapeptide,a bioactive peptide isolated from the gut of the earthworm." Cell Tissue Res.288. 567-573 (1997)
[Publications] Y.Furukawa: "Comparison of accumulative inactivation between the Aplysia K+ channel(AKyl.la) and its amino-terminal deletion mutant." Zool.Sci.14. 397-408 (1997)
[Publications] F.Morishita: "A novel D-amino-acid-containing peptide isolated from Aplysia heart." Biochem.Biophys.Res.Commun.240. 354-358 (1997)
[Publications] 筒井和義: "トピュクス:脳がステロイドをつくる -新しい概念の脳内分子、ニューロステロイドの発見と研究の現状" 生物科学ニュース. 305. Z20-Z23 (1997)
[Publications] 筒井和義: "脳がステロイドをつくる -新しい概念の脳内分子-" 広大フォーラム、開かれた学問. 333. 277-280 (1997)
[Publications] 筒井和義: "記憶解明へ一歩:ステロイド小脳プルキンエ細胞でも合成" 中国新聞. 5月10日. (1997)
[Publications] 筒井和義: "小脳でもステロイド合成:記憶の仕組み解明へ期待" 中日新聞、東京新聞. 5月20日. (1997)
[Publications] Y.Azumaya: "Localization of galanin and its binding sites in the quail brain." Brain Res.727. 187-195 (1996)
[Publications] D.Li: "An oviposition-inducing peptide;Isolation,localization,and function of avian galanin." Endocrinology. 137. 1618-1626 (1996)
[Publications] M.Takase: "Prolactin augments luteinizing hormone binding to rat Leydig cells in serum-free culture." J.Biosci.21. 511-517 (1996)
[Publications] Q.Jiang: "Differential effects of adrenocorticotropin in vivo on cytochrome P4502D16 and P450c17 in the guinea pig cortex." Endocrinology. 137. 4811-4816 (1996)
[Publications] S.Kominami: "Reconstitution of the steroidogenic pathway from cholrsterol to aldosterone in liposome membrane." Biochim.Biophys.Acta.1301. 199-206 (1996)
[Publications] Q.Jiang: "Expression and zonal distribution of CYP2D16 in guinea pig adrenal cortex:relationship to xebobiotic metabolism." Mol.Pharmacol.49. 458-461 (1996)
[Publications] S.Sakaki: "Molecular engineering study on electron transfer from NADPH-P450 reductase to rat mitochondrial P450c27 in yeast microsomes." J.Biol.Chem.271. 26209-26212 (1996)
[Publications] T.Yamazaki: "15-Lipoxygenase metabolites of arachidonic acid midiates adrenocorticotropin action in bovine adrenal steroidogenesis." Endocrinology. 137. 26209-26212 (1996)
[Publications] M.Yasuda: "Regulation of atrial contraction in the seawater-adapted eel." Comp.Biochem.Phys.113A. 165-172 (1996)
[Publications] 筒井和義: "総説:新しい概念の脳内分子、ニューロステロイド" 比較生理生化学. 13. 3-13 (1996)
[Publications] T.Yamazaki: "Kinetic analysis of successive reactions catalyzed by cytochrome P450_<17α-lyase>. In Oxygen Homeostasis and Its Dynamics." Springer-Verlag,Tokyo Ed by Y.Ishimura et al., 17 (1998)
[Publications] K.Tsutsui: "P450scc activity in the brain. In Perspectives in Avian Endocrinology." Journal of Endocrinology Ltd. Ed by S.Harvey & R.J.Etches, 10 (1997)
[Publications] K.Tsutsui: "Neurosteroids in the avian brain. In Frontiers in Environmenral and Metabolic Endocribology." The University of Burdwas Press Ed by K.Maitra, 10 (1997)
[Publications] Y.Azumaya: "Galanin and galanin receptors in the avian brain. In Environmental and Conservation Endocrinology." Macquarie University Press Ed by J.Joss, 2 (1996)
[Publications] K.Tsutsui: "Demonstration and localization of galanin receptors in the avian oviduct. In Environmental and Conservation Endocrinology." Macquarie University Press Ed by J.Joss, 2 (1996)
[Publications] D.Li: "Isolation,localization and function of galanin in the avian oviduct. In Environmental and Conservation Endocrinology." Macquarie University Press Ed by J.Joss, 2 (1996)

1997 Fiscal Year Annual Research Report

脳内ニューロステロイドの生合成制御機構と作用機構に関する研究

Principal Investigator

筒井 和義 広島大学, 総合科学部, 教授 (20163842)

Research Products

[Publications] Y.Azumaya: "Existence and localization of a splicing factor U2AF-like protein in the zebra finch brain." J.Exp.Zool.280(in press). (1998)

[Publications] T.Yamazaki: "Kinetic analysis of successive reaction catalyzed by bovine cytochrome p450_<17α,lyase>." Biochemistry. (in press). (1998)

[Publications] K.Ukena: "Cytochrome P450 side-cain cleavage enzyme (P450scc) in the cerebellar Purkinje neuron and its neonatal change in rats." Endocrinology. 139. 137-147 (1998)

[Publications] T.Niida: "Characterization of binding of the annelidan myoactive peptides,GGNG peptides,to tissues of the earthworm,Eisenia foetida." J.Exp.Zool.279. 562-570 (1997)

[Publications] M.Takase: "Inhibition of prolactin in the downregulation of testicular follicle-stimulating hormone receptors in mice." J.Exp.Zool.278. 234-242 (1997)

[Publications] T.Kotegawa: "Inhibitory role of opioid peptides in the regulation of aggressive and sexual behaviors in male Japanese quails." J.Exp.Zool.277. 146-154 (1997)

[Publications] K.Tsutsui: "Demonstration,localization,and development of galanin receptors in the quail oviduct." J.Exp.Zool.277. 57-65 (1997)

[Publications] K.Ukena: "Immunochemical demonstration of Eisenia tetradecapeptide,a bioactive peptide isolated from the gut of the earthworm." Cell Tissue Res.288. 567-573 (1997)

[Publications] Y.Furukawa: "Comparison of accumulative inactivation between the Aplysia K+ channel(AKyl.la) and its amino-terminal deletion mutant." Zool.Sci.14. 397-408 (1997)

[Publications] F.Morishita: "A novel D-amino-acid-containing peptide isolated from Aplysia heart." Biochem.Biophys.Res.Commun.240. 354-358 (1997)

[Publications] 筒井和義: "トピュクス:脳がステロイドをつくる -新しい概念の脳内分子、ニューロステロイドの発見と研究の現状" 生物科学ニュース. 305. Z20-Z23 (1997)

[Publications] 筒井和義: "脳がステロイドをつくる -新しい概念の脳内分子-" 広大フォーラム、開かれた学問. 333. 277-280 (1997)

[Publications] 筒井和義: "記憶解明へ一歩:ステロイド小脳プルキンエ細胞でも合成" 中国新聞. 5月10日. (1997)

[Publications] 筒井和義: "小脳でもステロイド合成:記憶の仕組み解明へ期待" 中日新聞、東京新聞. 5月20日. (1997)

[Publications] Y.Azumaya: "Localization of galanin and its binding sites in the quail brain." Brain Res.727. 187-195 (1996)

[Publications] D.Li: "An oviposition-inducing peptide;Isolation,localization,and function of avian galanin." Endocrinology. 137. 1618-1626 (1996)

[Publications] M.Takase: "Prolactin augments luteinizing hormone binding to rat Leydig cells in serum-free culture." J.Biosci.21. 511-517 (1996)

[Publications] Q.Jiang: "Differential effects of adrenocorticotropin in vivo on cytochrome P4502D16 and P450c17 in the guinea pig cortex." Endocrinology. 137. 4811-4816 (1996)

[Publications] S.Kominami: "Reconstitution of the steroidogenic pathway from cholrsterol to aldosterone in liposome membrane." Biochim.Biophys.Acta.1301. 199-206 (1996)

[Publications] Q.Jiang: "Expression and zonal distribution of CYP2D16 in guinea pig adrenal cortex:relationship to xebobiotic metabolism." Mol.Pharmacol.49. 458-461 (1996)

[Publications] S.Sakaki: "Molecular engineering study on electron transfer from NADPH-P450 reductase to rat mitochondrial P450c27 in yeast microsomes." J.Biol.Chem.271. 26209-26212 (1996)

[Publications] T.Yamazaki: "15-Lipoxygenase metabolites of arachidonic acid midiates adrenocorticotropin action in bovine adrenal steroidogenesis." Endocrinology. 137. 26209-26212 (1996)

[Publications] M.Yasuda: "Regulation of atrial contraction in the seawater-adapted eel." Comp.Biochem.Phys.113A. 165-172 (1996)

[Publications] 筒井和義: "総説:新しい概念の脳内分子、ニューロステロイド" 比較生理生化学. 13. 3-13 (1996)

[Publications] T.Yamazaki: "Kinetic analysis of successive reactions catalyzed by cytochrome P450_<17α-lyase>. In Oxygen Homeostasis and Its Dynamics." Springer-Verlag,Tokyo Ed by Y.Ishimura et al., 17 (1998)

[Publications] K.Tsutsui: "P450scc activity in the brain. In Perspectives in Avian Endocrinology." Journal of Endocrinology Ltd. Ed by S.Harvey & R.J.Etches, 10 (1997)

[Publications] K.Tsutsui: "Neurosteroids in the avian brain. In Frontiers in Environmenral and Metabolic Endocribology." The University of Burdwas Press Ed by K.Maitra, 10 (1997)

[Publications] Y.Azumaya: "Galanin and galanin receptors in the avian brain. In Environmental and Conservation Endocrinology." Macquarie University Press Ed by J.Joss, 2 (1996)

[Publications] K.Tsutsui: "Demonstration and localization of galanin receptors in the avian oviduct. In Environmental and Conservation Endocrinology." Macquarie University Press Ed by J.Joss, 2 (1996)

[Publications] D.Li: "Isolation,localization and function of galanin in the avian oviduct. In Environmental and Conservation Endocrinology." Macquarie University Press Ed by J.Joss, 2 (1996)

筒井和義広島大学, 総合科学部, 教授 (20163842)