Clinical investigation of 11 beta-hydroxysteroid dehydrogenase

Abstract

At least two isoforms of 11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD) have been identified, and clinical studies have illustrated their physiological and pathological significance. In the kidney, a high affinity 11 beta-OHSD2 inactivates cortisol to cortisone and protects mineralocorticoid receptors from cortisol. In the liver, a low affinity 11 beta-OHSD1 converts cortisone to cortisol, and may ensure that glucocorticoid receptors are adequately exposed to cortisol. In vascular smooth muscle, the conversion of cortisol to cortisone influences vascular tone. Defects in 11 beta-OHSD2 probably account for mineralocorticoid excess in the syndromes of Apparent Mineralocorticoid Excess, licorice administration, and ectopic ACTH syndrome. Defects in 11 beta-OHSD1 may be important in essential hypertension, and polycystic ovarian syndrome. The underlying mechanism for all of these defects, and the putative role of endogenous inhibitors of 11 beta-OHSD, remains unclear. In future, the measurement of the activity of individual isoforms should resolve this uncertainty.