Selective inhibition of human type 1 11β‐hydroxysteroid dehydrogenase by synthetic steroids and xenobiotics

FEBS Letters

Hult, Malin¹  Oppermann, Udo C.T¹  Jörnvall, Hans¹ 

[1] Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S-171 77 Stockholm, Sweden

关键词: 11β-Hydroxysteroid dehydrogenase;    Glucocorticoid;    Short-chain dehydrogenase/reductase;    Yeast expression;    Membrane protein;    11β-HSD-1;    11β-hydroxysteroid dehydrogenase type 1;    SDR;    short-chain dehydrogenases/reductases;    GA;    glycerrhitinic acid;    CBX;    carbenoxolone;    GC;    glucocorticoid;   

DOI  :  10.1016/S0014-5793(98)01515-4

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Functional analyses were performed with microsomal human 11β-hydroxysteroid dehydrogenase type 1 overexpressed in the yeast Pichia pastoris. Cell extracts or microsomes from transformed strains displayed dehydrogenase and reductase activities, which were up to 10 times higher than in human liver microsomes, while for whole cells cortisone reduction but no dehydrogenase activity was observed. The synthetic glucocorticoids prednisolone and prednisone were efficiently metabolized by subcellular fractions, whereas no activity was observed with dexamethasone, budesonide and deflazacort. Inhibitors found to be effective towards the recombinant 11β-hydroxysteroid dehydrogenase include synthetic steroids and xenobiotic compounds, revealing selective inhibition of the reaction direction, useful for development of specific inhibitors.

【 授权许可】

Unknown