A non-isotopic method for estimating 11 beta hydroxysteroid dehydrogenase activity in vivo.
11 beta-hydroxysteroid dehydrogenase (11 beta HSD) has both dehydrogenase (11 beta DH) and reductase (11 beta R) 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 radiolabelled cortisol 11 beta HSD activity has been shown to be lower in some cases of essential hypertension. This study investigated a novel approach to estimating 11 beta HSD activity in vivo. Plasma steroid kinetics were investigated following oral hydrocortisone (a substrate for 11 beta DH) and prednisone (a substrate for 11 beta R) in five normotensive volunteers after dexamethasone suppression of endogenous steroid production. This approach was evaluated by inducing partial deficiency of 11 beta HSD in the volunteers who took liquorice (to inhibit 11 beta DH) and then carbenoxolone (to inhibit both 11 beta DH and 11 beta R). The ratio of cortisol to prednisolone (formed from prednisone) provided a measure of the activity of both 11 beta DH and 11 beta R. At 75 min 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 11 beta HSD activity in vivo in large numbers of hypertensive patients without the use of radioisotopes.
Bayly
G R
GR
Department of Clinical Biochemistry, Birmingham Heartlands Hospital, UK.
Bartlett
W A
WA
Jones
A F
AF
D042842:11-beta-Hydroxysteroid Dehydrogenases; D002229:Carbenoxolone / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D003907:Dexamethasone / Q000097:blood; D006035:Glycyrrhiza; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D006913:Hydroxysteroid Dehydrogenases / Q000032:analysis* / Q000187:drug effects / Q000378:metabolism; D008297:Male; D010946:Plants, Medicinal; D011241:Prednisone / Q000097:blood; D013256:Steroids / Q000097:blood
D013256:Steroids; D003907:Dexamethasone; D006913:Hydroxysteroid Dehydrogenases; D042842:11-beta-Hydroxysteroid Dehydrogenases; D002229:Carbenoxolone; D011241:Prednisone; D006854:Hydrocortisone