CHARACTERIZATION OF 11-BETA-HSD1B GENE-EXPRESSION AND ENZYMATIC-ACTIVITY

Nuclease protection analysis has been used to study the distribution o f an mRNA that has been predicted to give rise to a truncated form of the enzyme 11beta-hydroxysteroid dehydrogenase (11beta-HSD1B). The 11b eta-HSD1B mRNA was found exclusively in the kidney, predominantly loca lized within the medulla with low amounts of the message in the cortex . Neither the renal papilla nor a range of peripheral and central tiss ues showed evidence of 11beta-HSD1B mRNA. Expression of the whole (11b eta-HSD1A) and truncated enzymes in COS cells resulted in immunoreacti ve 34 kDa and 26 kDa proteins respectively, while kidney homogenates s howed 34 kDa and 40 kDa species. The 11beta-HSD1A enzyme converted cor ticosterone and cortisol to their respective 11-dehydro metabolites wi th an absolute dependence on NADP as co-factor, while the 26 kDa 11bet a-HSD1B protein was unable to metabolize either steroid. These results suggest that transcription of the 11beta-HSD1B mRNA is associated wit h a mechanism down-regulating production of 11beta-HSD1 activity.