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ID 34762
本文ファイル
著者
Higo, Shimpei
Hojo, Yasushi
Ishii, Hirotaka
Komatsuzaki, Yoshimasa
Ooishi, Yuuki
Murakami, Gen
Mukai, Hideo
Nakahara, Daiichiro
Barron, Anna
Kimoto, Tetsuya
Kawato, Suguru
NDC
医学
抄録(英)
Background: Brain synthesis of steroids including sex-steroids is attracting much attention. The endogenous synthesis of corticosteroids in the hippocampus, however, has been doubted because of the inability to detect deoxycorticosterone (DOC) synthase, cytochrome P450(c21).

Methodology/Principal Findings: The expression of P450(c21) was demonstrated using mRNA analysis and immmunogold 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 5.8 nM, respectively. Enhanced spinogenesis was observed in the hippocampus following application of low nanomolar (10 nM) doses of CORT for 1 h.

Conclusions/Significance: These results imply the complete pathway of corticosteroid synthesis of ‘pregnenolone RPROGRDOCRCORT' in the hippocampal neurons. Both P450(c21) and P450(2D4) can catalyze conversion of PROG to DOC. The low nanomolar level of CORT synthesized in hippocampal neurons may play a role in modulation of synaptic plasticity, in contrast to the stress effects by micromolar CORT from adrenal glands.
掲載誌名
PLoS ONE
6巻
7号
開始ページ
e21631
出版年月日
2011
出版者
Public Library of Science
ISSN
1932-6203
出版者DOI
言語
英語
NII資源タイプ
学術雑誌論文
広大資料タイプ
学術雑誌論文
DCMIタイプ
text
フォーマット
application/pdf
著者版フラグ
publisher
権利情報
(c) 2011 Higo et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
関連情報URL
部局名
総合科学研究科