Substrate and inhibitor specificity of the cloned human 11[beta]
-hydroxysteroid dehydrogenase type 2 isoform.
Ferrari, Paolo, Robin E. Smith, John W. Funder, and Zygmunt S.
Krozowski.
Baker Medical Research Institute, Melbourne, Australia
APStracts 3:0004E, 1996.
The 11[beta]-hydroxysteroid dehydrogenase type II (11[beta]HSD2)
enzyme is thought to confer specificity on the mineralocortiocid
receptor by inactivating glucocorticoids in mineralocortiocid target
organs. The cloned 11[beta]HSD2 displayed K[mu] values for
corticosterone and cortisol of 5.1 and 61 nM, respectively. Linearity
in the dose-response curve ranged between 1 to 200 nM for
corticosterone and 25 to 2000 nM for cortisol, with no evidence for
complex kinetics. Inhibition of cortisol oxidation by other steroids
was purely competitive in nature. Inhibition of 11[beta]HSD2 activity
by the end-product or aldosterone occured only at supraphysiological
levels, whereas corticosterone and deoxycorticosterone displayed
significant inhibition at physiological concentrations, and
progesterone at concentrations which occur during pregnancy. In
intact transfected CHOP cells dexamethasone was converted to 11
-dehydrodexamethasone by 11[beta]HSD2 but not 11[beta]HSD1, an aspect
that may be useful in evaluating 11[beta]HSD activity in intact
cells.
Received 7 June 1995; accepted in final form 13 December 1995.
APS Manuscript Number E262-5.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 22 January 96