Physiologic roles of 11β-hydroxysteroid dehydrogenase type 2 in kidney

We developed enzyme-linked immunosorbent assays to measure urinary free cortisone (E) and cortisol (F) and analyzed correlations between clinical measures reflecting mineralocorticoid action and 24-hour urinary excretion of E and F or their ratio, uE/F, which has been considered as the most sensitive index of renal 11β-hydroxysteroid dehydrogenase type 2 activity. Two hundred nineteen healthy men were enrolled in this study. The uE/F ratio was 1.10 ± 0.41 (mean ± SD), and a strong linear correlation between uE and uF was observed in a double reciprocal plot. Urinary acid-labile aldosterone excretion had a negative correlation with 24-hour urinary Na excretion and Na/K ratio, but uE/F ratio had a weak positive correlation with the Na/K ratio and no significant correlation with 24-hour urinary Na excretion. In contrast, uE and uF had positive correlations with 24-hour urinary excretions of Na and K, raising the possibility of separate renal effects mediated by the glucocorticoid receptor. Furthermore, uE and uE/F ratio had strong negative correlations with urinary concentrations of Na and K. These results suggest that renal 11β-hydroxysteroid dehydrogenase type 2 is an important regulatory factor of renal Na and K handlings independently of and/or complementary to the mineralocorticoid action of aldosterone.