CLONING, SEQUENCING AND TISSUE-DISTRIBUTION OF MOUSE 11-BETA-HYDROXYSTEROID DEHYDROGENASE-1 CDNA

11 beta-Hydroxysteroid dehydrogenase (11 beta-HSD) reversibly converts physiological glucocorticoids (cortisol, corticosterone) to inactive Il-dehydro forms, and thus controls glucocorticoid access to receptors in a variety of tissues. We have cloned a cDNA encoding 'liver-type' 11 beta-HSD (11 beta-HSD1) from the mouse using PCR, and have determined its nucleotide sequence. Mouse 11 beta-HSD1 cDNA showed 91% identity to rat 11 beta-HSD1 cDNA. There was 87% amino acid identity with rat 11 beta-HSD1 with conservation of the putative cofactor and substrate binding domains. Northern blot analysis of mouse tissues demonstrated abundant 11 beta-HSD1 message in the liver, kidney and lung, with lower expression in brain subregions and gonads. 11 beta-HSD1 mRNA was below the level of detection in the murine colon. 11 beta-HSD1 mRNA levels in kidney was higher in males than in females, but in contrast to the rat, there was no sexual dimorphism in the mouse liver. Although males and females showed different mRNA levels in the kidney, there was no sex difference in 11 beta-HSD enzyme activity. Thus, despite the high inter-species conservation of 11 beta-HSD1, there are clear species and tissue-specific differences in its expression.