Tissue- and temporal-specific regulation of 11beta-hydroxysteroid dehydrogenase type 1 by glucocorticoids in vivo

P M Jamieson, K E Chapman, J R Seckl

Research output: Contribution to journalArticlepeer-review

Abstract

11Beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD-1) catalyses the interconversion of active corticosterone and inert 11-dehydrocorticosterone. Short-term glucocorticoid excess upregulates 11beta-HSD-1 in liver and hippocampus leading to suggestions that 11beta-HSD-1 ameliorates the deleterious effects of glucocorticoid excess by its 11beta-dehydrogenase activity. However the predominant activity of 11beta-HSD-1 in vivo is 11beta-reduction, thus generating active glucocorticoid. We have re-examined the time-course of glucocorticoid regulation of 11beta-HSD-1 in the liver, hippocampus and kidney of adult male rats in vivo. Sham operation markedly reduced 11beta-HSD-1 mRNA expression in all tissues, and reduced 11beta-HSD bioactivity in liver and hippocampus when compared to untouched controls. Adrenalectomy reduced 11beta-HSD-1 expression in all tissues in the short-term (7 days), followed by subsequent recovery of enzyme activity by 21 days in liver and hippocampus. Dexamethasone replacement of adrenalectomised rats attenuated the initial decrease in hepatic 11beta-HSD-1 activity, but by 21 days dexamethasone reduced activity compared to control levels. Thus glucocorticoids regulate 11beta-HSD-1 in a complex tissue- and temporal-specific manner. This pattern of regulation suggests glucocorticoids repress 11beta-HSD-1 at least in the liver, a pattern of regulation more consistent with the evidence that 11beta-HSD-1 is an 11beta-reductase in vivo. Operational stress per se down-regulates 11beta-HSD-1 which has implications for interpretation and design of in vivo studies of 11beta-HSD-1.

Original languageEnglish
Pages (from-to)245-50
Number of pages6
JournalJournal of Steroid Biochemistry and Molecular Biology
Volume68
Issue number5-6
Publication statusPublished - Mar 1999

Keywords

  • 11-beta-Hydroxysteroid Dehydrogenases
  • Adrenalectomy
  • Animals
  • Enzyme Induction
  • Gene Expression Regulation
  • Glucocorticoids
  • Hippocampus
  • Hydroxysteroid Dehydrogenases
  • Kidney
  • Liver
  • Male
  • RNA, Messenger
  • Rats
  • Rats, Wistar
  • Time Factors

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