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 determin ed its nucleotide sequence. Mouse 11 beta-HSD1 cDNA showed 91% identit y 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 low er expression in brain subregions and gonads. 11 beta-HSD1 mRNA was be low the level of detection in the murine colon. 11 beta-HSD1 mRNA leve ls in kidney was higher in males than in females, but in contrast to t he rat, there was no sexual dimorphism in the mouse liver. Although ma les and females showed different mRNA levels in the kidney, there was no sex difference in 11 beta-HSD enzyme activity. Thus, despite the hi gh inter-species conservation of 11 beta-HSD1, there are clear species and tissue-specific differences in its expression.