ISSN:
1365-2826
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Medicine
Notes:
Chronic glucocorticoid excess or deficiency is associated with hippocampal dysfunction and neuronal death. 11β-hydroxysteroid dehydro-genase (11β-OHSD), which catalyses the reversible conversion of corticosterone to inactive 11 -dehydrocorticosterone, regulates glucocorticoid access to receptors in the kidney and liver in vivo. The enzyme is also present in the hippocampus where it might modulate glucocorticoid action. We examined the effects of corticosteroid manipulations on hippocampal and peripheral 11β-OHSD. In the hippocampus, chronic adrenalectomy (10 days) had no effect on 11β-OHSD activity, compared to sham-operated controls. Treatment of adrenalectomized animals with dexamethasone (200 μg/kg.day−1), but not aldosterone (20 μg/kg.day−1), for 10 days significantly increased hippocampal 11β-OHSD activity compared with sham or adrenalectomized rats (22% and 23% rise respectively, P〈0.05). These effects reflect changes in transcription of the liver-type 11β-OHSD gene, with dexamethasone significantly increasing 11β-OHSD mRNA expression in the hippocampus compared with sham or adrenalectomized animals (32% and 70% higher respectively, P〈0.05). In the liver, adrenalectomy significantly reduced 11β-OHSD activity (16% lower), which was restored to sham levels by dexamethasone, but not aldosterone. Similar trends were seen in 11β-OHSD mRNA expression, although these did not reach significance. None of the manipulations altered 11β-OHSD activity or mRNA expression in the kidney. The hippocampal effects of dexamethasone were similar to those of chronic stress (arthritis) which increased 11β-OHSD activity (20% rise, P〈0.05), although this was not reflected at the level of mRNA. Thus, hippocampal (and hepatic, but not renal) 11β-OHSD appears to be regulated by chronic glucocorticoid manipulations and stress. Hippocampal 11β-OHSD may thus ensure optimal long-term corticosterone exposure of glucocorticoid-sensitive neurons.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1111/j.1365-2826.1994.tb00584.x
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