PMID- 8866246
OWN - NLM
STAT- MEDLINE
DCOM- 19970115
LR  - 20141120
IS  - 0953-8194 (Print)
IS  - 0953-8194 (Linking)
VI  - 8
IP  - 8
DP  - 1996 Aug
TI  - 11 beta-Hydroxysteroid dehydrogenase activity in the hippocampus: implications 
      for in vivo corticosterone receptor binding and cell nuclear retention.
PG  - 595-600
AB  - In this study a possible role of 11 beta-hydroxysteroid dehydrogenase (11 
      beta-HSD) in altering the access of corticosteroids to their receptors in the 
      hippocampus is investigated. In vitro, oxidation of corticosterone to 
      11-dehydrocorticosterone (11-DHC) was demonstrated in hippocampal homogenates. 
      Glycyrrhetinic acid (GE) and carbenoxolone (CBX) were potent inhibitors of 11 
      beta-HSD activity and did not display affinity for mineralocorticoid (MRs) nor 
      glucocorticoid receptors (GRs). Intracerebroventricular injection of CBX in vivo 
      (ED50 approximately 30 micrograms) decreased oxidative activity in hippocampal 
      homogenates, as demonstrated in vitro. In vitro, in hippocampal slices, cell 
      nuclear retention of tritiated corticosterone, but not aldosterone, was markedly 
      enhanced in the presence of GE, which at a concentration of 20 nM was found to 
      inhibit 11 beta-HSD activity by about 50% in the intact cell preparation. In 
      contrast to the effect on in vitro cell nuclear uptake, in vivo autoradiography 
      revealed that retention of corticosterone in the hippocampal cell nuclei was not 
      affected after intracerebroventricular treatment with CBX. We conclude that 
      hippocampal 11 beta-HSD activity does not alter binding of low amounts of 
      corticosterone to MRs in vivo, but we cannot exclude that the enzyme may modulate 
      access to corticosteroid receptors under certain circumstances.
FAU - van Haarst, A D
AU  - van Haarst AD
AD  - Department of Medical Pharmacology, Liden-Amsterdam Center for Drug Research, 
      Leiden University, The Netherlands.
FAU - Welberg, L A
AU  - Welberg LA
FAU - Sutanto, W
AU  - Sutanto W
FAU - Oitzl, M S
AU  - Oitzl MS
FAU - de Kloet, E R
AU  - de Kloet ER
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Neuroendocrinol
JT  - Journal of neuroendocrinology
JID - 8913461
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Receptors, Steroid)
RN  - 0 (corticosterone receptor)
RN  - EC 1.1.- (Hydroxysteroid Dehydrogenases)
RN  - EC 1.1.1.146 (11-beta-Hydroxysteroid Dehydrogenases)
RN  - FO4V44A3G3 (11-dehydrocorticosterone)
RN  - MM6384NG73 (Carbenoxolone)
RN  - P540XA09DR (Glycyrrhetinic Acid)
RN  - W980KJ009P (Corticosterone)
SB  - IM
MH  - 11-beta-Hydroxysteroid Dehydrogenases
MH  - Animals
MH  - Autoradiography
MH  - Carbenoxolone/pharmacology
MH  - Cell Nucleus/*metabolism
MH  - Corticosterone/analogs & derivatives/*metabolism
MH  - Enzyme Inhibitors/pharmacology
MH  - Glycyrrhetinic Acid/pharmacology
MH  - Hippocampus/cytology/enzymology/*metabolism
MH  - Hydroxysteroid Dehydrogenases/antagonists & inhibitors/*metabolism
MH  - In Vitro Techniques
MH  - Male
MH  - Rats
MH  - Rats, Wistar
MH  - Receptors, Steroid/*metabolism
MH  - Regression Analysis
EDAT- 1996/08/01 00:00
MHDA- 1996/08/01 00:01
CRDT- 1996/08/01 00:00
PHST- 1996/08/01 00:00 [pubmed]
PHST- 1996/08/01 00:01 [medline]
PHST- 1996/08/01 00:00 [entrez]
PST - ppublish
SO  - J Neuroendocrinol. 1996 Aug;8(8):595-600.