In the human and in rodents like the rat and mouse, the liver enzyme 11β-hydroxysteroid dehydrogenase type I (11β-HSD-I) is a functional oxidoreductase preferring NADP+/NADPH as cosubstrate, while the renal isoenzyme (11β-HSD-II) prefers NAD+ as cosubstrate, and seems to be a pure oxidase and protects the tubular mineralocorticoid (MC) receptor from occupancy by cortisol and corticosterone. We studied the enzyme kinetics of 11β-HSDs in kidney and liver microsomes of the guinea pig, a species whose zoological classification is still a matter of debate. With a fixed concentration of 10−6 mol/l cortisol, liver and kidney microsomes preferred NAD+ to NADP+ (10−3 mol/l) for the conversion to cortisone. Kidney microsomes converted cortisol to cortisone with K m values of 0·64 μmol/l and 9·8 μmol/l with NAD+ and NADP+ as cosubstrates respectively. The reduction of cortisone to cortisol was slow with kidney microsomes, but could be markedly enhanced by adding an NADH/NADPH regenerating system: with NADPH as preferred cosubstrate, the approximate K m was 7·2 μmol/l. This indicated the existence of both isoenzymes in the guinea pig kidney. Liver microsomes oxidized cortisol to cortisone with similar K m and Vmax values for NAD+ to NADP+ as cosubstrates (K m of 4·3 μmol/l and 5·0 μmol/l respectively). The NAD+ preference for the oxidation of 10−6 mol/l cortisol described above may be due to a second, NAD+-preferring 11β-HSD with a K m of 1·4 μmol/l. In contrast to the kidney, liver microsomes actively converted cortisone to cortisol with a preference for NADPH (K m: 1·2 μmol/l; Vmax: 467 nmol/min per mg protein). Thus, the main liver enzyme is similar to the oxidoreductase of other species (11β-HSD-I) and is also present in the kidney, while the main kidney enzyme is clearly NAD+-preferring. This kidney enzyme (analogous to 11β-HSD-II of other species) seems to be suitable for the protection of the MC receptor from the high free plasma cortisol levels of the guinea pig.
Journal of Endocrinology (1997) 153, 291–298