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

11 -Hydroxysteroid dehydrogenase type 1 (11 -HSD-1), a regulator of intrahepatocellular glucocorticoid activity, is bidirectional in homogenates but catalyses 11 reduction (regenerating glucocorticoid) in intact primary hepatocytes in culture. To examine this discrepancy at the whole-organ level, we examined 11 -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 -reduced to corticosterone, whereas 10 1% of corticosterone was 11 -dehydrogenated to 11-DHC. 11 -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 -Reductase activity was not saturated by 11-DHC (10 -10 6 M). Perfusion with carbenoxolone (CBX, 10 -10 3 M) did not alter 11 reduction of 11-DHC. In contrast, pretreatment with CBX in vivo (10 mg/day) for 7 days inhibited 11 reductase (19 4% conversion, P<0·01). Concentrations of 11-DHC in male rat plasma were 44 6 nM. Thus 11 -HSD-1 is predominantly an 11 -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 -HSD-1 activity and its potential selective inhibition could modify glucocorticoid action in vivo. Journal of Endocrinology (2000) 165, 685–692