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11 β ‐Hydroxysteroid Dehydrogenase Activity in the Hippocampus: Implications for in vivo Corticosterone Receptor Binding and Cell Nuclear Retention
Author(s) -
van Haarst Aernout D.,
Welberg Leonie A. M.,
Sutanto Win,
Oitzl Melly S.,
Ron de Kloet E.
Publication year - 1996
Publication title -
journal of neuroendocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.062
H-Index - 116
eISSN - 1365-2826
pISSN - 0953-8194
DOI - 10.1111/j.1365-2826.1996.tb00693.x
Subject(s) - carbenoxolone , corticosterone , endocrinology , medicine , hippocampal formation , in vivo , receptor , glucocorticoid receptor , mineralocorticoid , chemistry , glucocorticoid , in vitro , mineralocorticoid receptor , aldosterone , biology , biochemistry , hormone , microbiology and biotechnology , gap junction , intracellular
In this study a possible role of 11 β ‐hydroxysteroid dehydrogenase (11 β ‐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 β ‐HSD activity and did not display affinity for mineralocorticoid (MRs) nor glucocorticoid receptors (GRs). Intracerebroventricular injection of CBX in vivo (ED 50 ∼30 μg) 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 β ‐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.