title: Endogenous synthesis of corticosteroids in the hippocampus.
abstract: 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).
  
  
  RESULTS
  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 (3)H-steroids. All the enzymes required for corticosteroid synthesis including P450(c21), P450(2D4), P450(11β1) and 3β-hydroxysteroid dehydrogenase (3β-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
  These results imply the complete pathway of corticosteroid synthesis of 'pregnenolone →PROG→DOC→CORT' 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.
authors.affiliation: Department of Biophysics and Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, Meguro, Tokyo, Japan.
authors.forename: Shimpei
authors.initials: S
authors.lastname: Higo
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Hojo
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Ishii
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Komatsuzaki
authors.forename: Yuuki
authors.initials: Y
authors.lastname: Ooishi
authors.forename: Gen
authors.initials: G
authors.lastname: Murakami
authors.forename: Hideo
authors.initials: H
authors.lastname: Mukai
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yamazaki
authors.forename: Daiichiro
authors.initials: D
authors.lastname: Nakahara
authors.forename: Anna
authors.initials: A
authors.lastname: Barron
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Kimoto
authors.forename: Suguru
authors.initials: S
authors.lastname: Kawato
mesh_terms: D000818:Animals; D015139:Blotting, Southern; D002853:Chromatography, Liquid; D003345:Corticosterone / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism; D003900:Desoxycorticosterone / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D017403:In Situ Hybridization; D008297:Male; D016253:Microscopy, Immunoelectron; D011374:Progesterone / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D012333:RNA, Messenger; D003900:Desoxycorticosterone; D011374:Progesterone; D003577:Cytochrome P-450 Enzyme System; D003345:Corticosterone