CLINICAL INVESTIGATION OF 11-BETA-HYDROXYSTEROID DEHYDROGENASE

At least two isoforms of 11 beta-hydroxysteroid dehydrogenase (11 beta -OHSD) have been identified, and clinical studies have illustrated the ir 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 affinit y 11 beta-OHSD1 converts cortisone to cortisol, and may ensure that gl ucocorticoid receptors are adequately exposed to cortisol. In vascular smooth muscle, the conversion of cortisol to cortisone influences vas cular tone. Defects in 11 beta-OHSD2 probably account for mineralocort icoid excess in the syndromes of Apparent Mineralocorticoid Excess, li corice administration, and ectopic ACTH syndrome. Defects in 11 beta-O HSD1 may be important in essential hypertension, and polycystic ovaria n syndrome. The underlying mechanism for all of these defects, and the putative role of endogenous inhibitors of 11 beta-OHSD, remains uncle ar. In future, the measurement of the activity of individual isoforms should resolve this uncertainty.