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

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