Selective inhibition of human type 1 11 beta-hydroxysteroid dehydrogenase by synthetic steroids and xenobiotics

Functional analyses were performed with microsomal human 11 beta-hydroxyste roid dehydrogenase type 1 overexpressed in the yeast Pichia pastor is. Cell extracts or microsomes from transformed strains displayed dehydrogenase an d reductase activities, which were up to 10 times higher than in human live r microsomes, while for whole cells cortisone reduction but no dehydrogenas e activity was observed. The synthetic glucocorticoids prednisolone and pre dnisone were efficiently metabolized by subcellular fractions, whereas no a ctivity was observed with dexamethasone, budesonide and deflazacort. Inhibi tors found to be effective towards the recombinant 11 beta-hydroxysteroid d ehydrogenase include synthetic steroids and xenobiotic compounds, revealing selective inhibition of the reaction direction, useful for development of specific inhibitors. (C) 1998 Federation of European Biochemical Societies.