Abstract
11 β-hydroxysteroid dehydrogenase (11βHSD) has both dehydrogenase (11βDH) and reductase (11βR) activities, which catalyse the interconversion of Cortisol and cortisone, and prednisolone and prednisone. This enzyme confers specificity on the mineralocorticoid receptor by local oxidation of Cortisol to cortisone. Using radiolabeled Cortisol 11βHSD activity has been shown to be lower in some cases of essential hypertension. This study investigated a novel approach to estimating 11βHSD activity in vivo. Plasma steroid kinetics were investigated following oral hydrocortisone (a substrate for 11βDH) and prednisone (a substrate for 11βR) in five normotensive volunteers after dexamethasone suppression of endogenous steroid production. This approach was evaluated by inducing partial deficiency of 11βHSD in the volunteers who took liquorice (to inhibit 11βDH) and then carbenoxolone (to inhibit both 11βDH and 11βR). The ratio of Cortisol to prednisolone (formed from prednisone) provided a measure of the activity of both 11βDH and 11βR. At 75min after the steroid bolus the ratio increased from 1·1 (0·6–1·3) (median, range) under control conditions to 1·2 (0·8–1·7) after liquorice (P = 0·01, n = 5), and 2·0 (1·3–5·9) after carbenoxolone (P = 0·02, n = 5). It may therefore be applied to the measurement of 11βHSD activity in vivo in large numbers of hypertensive patients without the use of radioisotopes.