Effects of bile acids on rat hepatic microsomal type I 11β-hydroxysteroid dehydrogenase

The aim of this study was to investigate the effect of various bile acids on hepatic type I 11β-hydroxysteroid dehydrogenase (11β-HSD1) activity in vitro. The rat liver microsome fraction was prepared and 11β-HSD1 activity was assayed using cortisol and corticosterone as substrates for the enzyme reaction. The substrate and various concentrations of bile acids were added to the assay mixture. After incubation, the products were extracted and analyzed using high-performance liquid chromatography. All bile acids tested except deoxycholic acid and 7-keto bile acids inhibited the 11β-HSD1 enzyme reaction to some degree. Ursodeoxycholic acid inhibited the activity less than cholic, chenodeoxycholic, and lithocholic acids. Deoxycholic acid and 7-keto bile acids did not inhibit, but enhanced the enzyme activity. Inhibitions of dehydrogenation by corticosterone were weaker than those by cortisol. Kinetic analysis revealed that the inhibition of 11β-HSD1 was competitive. The inhibition of 11β-HSD1 by bile acids depended on the three-dimensional structural difference in the steroid rings and the presence of the 7α-hydroxy molecule of the bile acids was important for the inhibition of rat hepatic 11β-HSD1 enzyme activity. These results suggest that bile acid administration might modulate 11β-HSD1 enzyme activity.