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11 beta-Hydroxysteroid dehydrogenase type 1 is a predominant 11 beta-reductase in the intact perfused rat liver

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Original languageEnglish
Pages (from-to)685-692
Number of pages8
JournalJournal of Endocrinology
Volume165
Issue number3
DOIs
Publication statusPublished - Jun 2000

Abstract

11 beta-Hydroxysteroid dehydrogenase type 1 (11 beta-HSD-1), a regulator of intrahepatocellular glucocorticoid activity, is bidirectional in homogenates but catalyses 11 beta-reduction (regenerating glucocorticoid) in intact primary hepatocytes in culture. To examine this discrepancy at the whole-organ level, we examined 11 beta-HSD-1 activity in the intact bivascularly perfused rat liver. On a single pass through male rat Liver, 44 +/- 5% of 11-dehydrocorticosterone (11-DHC) recovered was 11 beta-reduced to corticosterone, whereas 10 +/- 1% of corticosterone was 11 beta-dehydrogenated to 11-DHC. 11 beta-Reduction was less in female liver (21 +/- 2%, P < 0.01) and was significantly greater with perfusion of all substrate via the portal vein (50 +/- 3%) than via the hepatic artery (30 +/- 2%, P < 0.05). 11 beta-Reductase activity was not saturated by 11-DHC (10(-9)-10(-6) M). Perfusion with carbenoxolone (CBX, 10(-6)-10(-3) M) did not alter 11 beta-reduction of 11-DHC. In contrast, pretreatment with CBX in vivo (10 mg/day) for 7 days inhibited 11 beta-reductase (19 +/- 3% conversion, P < 0.01). Concentrations of 11-DHC in male rat plasma were 44 +/- 6 nM. Thus 11 beta-HSD-1 is predominantly an 11 beta-reductase in the intact rat liver and is only inhibited by chronic administration of CBX. The substantial concentrations of plasma 11-DHC as substrate suggest that 11 beta-HSD-1 activity and its potential selective inhibition could modify glucocorticoid action in vivo.

    Research areas

  • 11-beta-Hydroxysteroid Dehydrogenases, Animals, Carbenoxolone, Corticosterone, Dose-Response Relationship, Drug, Female, Hydroxysteroid Dehydrogenases, Liver, Male, Rats, Sex Characteristics

ID: 2385586