Clinical investigation of 11β-hydroxysteroid dehydrogenase

Abstract

At least two isoforms of 11β-hydroxysteroid dehydrogenase (11β-OHSD) have been identified, and clinical studies have illustrated their physiological and pathological significance. In the kidney, a high affinity 11β-OHSD₂ inactivates cortisol to cortisone and protects mineralocorticoid receptors from cortisol. In the liver, a low affinity 11β-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 11β-OHSD₂ probably account for mineralocorticoid excess in the syndromes of Apparent Mineralocorticoid Excess, licorice administration, and ectopic ACTH syndrome. Defects in 11β-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 11β-OHSD, remains unclear. In future, the measurement of the activity of individual isoforms should resolve this uncertainty.