Cloning and Primary Structure of Murine 11β‐Hydroxysteroid Dehydrogenase/Microsomal Carbonyl Reductase

Abstract

Screening of a mouse liver Agt 11 cDNA library with a rat liver 1lP-hydroxysteroid dehydrogenase cDNA (11P-HSDrlA) and subsequent screening with an isolated mouse probe, resulted in the isolation and structure determination of a mouse cDNA encoding an amino acid sequence which is very similar to human and rat 11P-hydroxysteroid dehydrogenases (78 % and 86 % similar, respectively), and also to other known vertebrate 1 lP-hydroxysteroid dehydrogenase structures. Open-reading-frame analysis and the deduced amino acid sequence predict a protein with a molecular mass of 32.3 kDa which beIongs to the superfamily of the short-chain dehydrogenase proteins. The amino acid sequence contains two potential glycosylation sites. These data are in agreement with information on the glycoprotein character of the native enzyme. This kind of post-translational modification seems to be a determining factor concerning the equilibrium of the catalyzed llP-dehydrogenation/ll -ox0 reduction step [Obeid,

Type 1 11β-Hydroxysteroid Dehydrogenase Mediates Glucocorticoid Activation and Insulin Release in Pancreatic Islets

“…2A). An RT-PCR product of a size identical to that from liver was obtained using specific mouse primer sets (29), indicating expression of type 1 11␤-HSD in pancreatic islets. The same set of experiments was performed with RNA isolated from human islets (Fig.…”

Comparative enzymology of 11β-hydroxysteroid dehydrogenase type 1 from six species

“…In addition to the previously characterized hamster, rat and human 11 -HSD1 enzymes , we have now cloned 11 -HSD1 from mouse and guinea pig with oligonucleotide primers based on sequences available from GenBank (Oppermann et al 1995, Rajan et al 1995. The murine sequence was identical to that present in GenBank.…”

“…The cloning of human (Tannin et al 1991), rat (Agarwal et al 1989), mouse (Oppermann et al 1995, Rajan et al 1995 and guinea-pig 11 -HSD1 cDNA (Pu & Yang 2000) has been reported earlier, as has the construction of untagged and FLAG epitope-tagged human, rat and hamster 11 -HSD1 (Odermatt et al 1999. Mouse and guinea-pig 11 -HSD1 were amplified by PCR using specific oligonucleotide primers based on available sequences from GenBank.…”

Human 11β-Hydroxysteroid Dehydrogenase Type 1 Is Enzymatically Active in Its Nonglycosylated Form

“…Although mice deficient in 11␤-HSD 1 were found to resist hyperglycemia provoked by obesity or stress (6), the physiological function of this enzyme is still not clear. In recent investigations it could be shown that 11␤-HSD 1 plays an important role in xenobiotic carbonyl reduction (7)(8)(9)(10).…”