Endogenous Synthesis of Corticosteroids in the Hippocampus 英文参考文献.docVIP

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Endogenous Synthesis of Corticosteroids in the Hippocampus 英文参考文献.doc

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Endogenous Synthesis of Corticosteroids in the Hippocampus 英文参考文献

EndogenousSynthesisofCorticosteroidsinthe Hippocampus ShimpeiHigo1.,YasushiHojo1,2,3.,HirotakaIshii1,YoshimasaKomatsuzaki1,4,YuukiOoishi1 ,Gen Murakami1,3,HideoMukai1,2,3,TakeshiYamazaki5,DaiichiroNakahara6,AnnaBarron1,TetsuyaKimoto1, SuguruKawato1,2,3 * 1Department of Biophysicsand Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, Meguro, Tokyo, Japan, 2Core Research for Evolutional ScienceandTechnologyProjectofJapanScienceandTechnologyAgency,TheUniversityofTokyo,Meguro,Tokyo,Japan,3BioinformaticsProjectofJapanScienceand Technology Agency, The University of Tokyo, Meguro, Tokyo, Japan, 4Department of Physics, College of Science and Technology, Nihon University, Chiyoda, Tokyo, Japan, 5Laboratory of Molecular Brain Science, Graduate School of Integrated Arts and Sciences, Hiroshima University, Higashi-Hiroshima, Japan, 6Department of Psychology,HamamatsuUniversitySchoolofMedicine,Hamamatsu,Japan Abstract Background:Brainsynthesisofsteroidsincludingsex-steroidsisattractingmuchattention.Theendogenoussynthesisof corticosteroids in the hippocampus, however, has been doubted because of the inability to detect deoxycorticosterone (DOC)synthase,cytochromeP450(c21). Methodology/PrincipalFindings:TheexpressionofP450(c21)wasdemonstratedusingmRNAanalysisandimmmunogold electron microscopic analysis in the adult male rat hippocampus. DOC production from progesterone (PROG) was demonstrated by metabolism analysis of 3H-steroids. All the enzymes required for corticosteroid synthesis including P450(c21), P450(2D4), P450(11b1) and 3b-hydroxysteroid dehydrogenase (3b-HSD) were localized in the hippocampal principal neurons as shown via in situ hybridization and immunoelectron microscopic analysis. Accurate corticosteroid concentrations in rat hippocampus were determined by liquid chromatography-tandem mass spectrometry. In adrenalectomized rats, net hippocampus-synthesized corticosterone (CORT) and DOC were determined to 6.9 and 5.8nM, respectively. En