S. Diederich, E. Eigendorff, Patrick Burkhardt
Dec 1, 2002
Citations
3
Influential Citations
137
Citations
Quality indicators
Journal
The Journal of Clinical Endocrinology and Metabolism
Abstract
The 11β-hydroxysteroid dehydrogenase (11β-HSD) system plays a pivotal role in glucocorticoid (GC) and mineralocorticoid (MC) action. Although 11β-HSD activities are important determinants for the efficacy of synthetic MCs and GCs, corresponding pharmacokinetic data are scanty. Therefore, we characterized 11β-HSD profiles for a wide range of steroids often used in clinical practice. 11β-HSD1 and 11β-HSD2 were selectively examined in 1) human liver and kidney cortex microsomes, and 2) Chinese hamster ovarian cells stably transfected with 11β-HSD1 or 11β-HSD2 expression vectors. Both systems produced concordant evidence for the following conclusions. Oxidation of steroids by 11β-HSD2 is diminished if they are fluorinated in position 6α or 9α (e.g. in dexamethasone) or methylated at 2α or 6α (in methylprednisolone) or 16α or 16β, by a methylene group at 16 (in prednylidene), methyloxazoline at 16, 17 (in deflazacort), or a 2-chlor configuration. Whereas the methyl groups also decrease reductase activity (ster...