{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T19:28:38Z","timestamp":1790364518426,"version":"4.1.0"},"reference-count":33,"publisher":"The Endocrine Society","issue":"12","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2002,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The 11\u03b2-hydroxysteroid dehydrogenase (11\u03b2-HSD) system plays a pivotal role in glucocorticoid (GC) and mineralocorticoid (MC) action. Although 11\u03b2-HSD activities are important determinants for the efficacy of synthetic MCs and GCs, corresponding pharmacokinetic data are scanty. Therefore, we characterized 11\u03b2-HSD profiles for a wide range of steroids often used in clinical practice. 11\u03b2-HSD1 and 11\u03b2-HSD2 were selectively examined in 1) human liver and kidney cortex microsomes, and 2) Chinese hamster ovarian cells stably transfected with 11\u03b2-HSD1 or 11\u03b2-HSD2 expression vectors. Both systems produced concordant evidence for the following conclusions.<\/jats:p><jats:p>Oxidation of steroids by 11\u03b2-HSD2 is diminished if they are fluorinated in position 6\u03b1 or 9\u03b1 (e.g. in dexamethasone) or methylated at 2\u03b1 or 6\u03b1 (in methylprednisolone) or 16\u03b1 or 16\u03b2, 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 (steric effects), fluorination increases reductase activity (negative inductive effect), leading to a shift to reductase activity. This may explain the strong MC activity of 9\u03b1-fluorocortisol and should be considered in GC therapy directed to 11\u03b2-HSD2-expressing tissues (kidney, colon, and placentofetal unit). 11\u03b2-HSD2 oxidation of prednisolone is more effective than that of cortisol, explaining the reduced MC activity of prednisolone compared with cortisol.<\/jats:p><jats:p>Reduction by 11\u03b2-HSD1 is diminished by 16\u03b1-methyl, 16\u03b2-methyl, 2\u03b1-methyl, and 2-chlor substitution, whereas it is increased by the \u03941-dehydro configuration in prednisone, resulting in higher hepatic first pass activation of prednisone compared with cortisone.<\/jats:p><jats:p>To characterize a GC or a MC as substrate for the different 11\u03b2HSDs may be essential for an optimized steroid therapy.<\/jats:p>","DOI":"10.1210\/jc.2002-020970","type":"journal-article","created":{"date-parts":[[2002,12,5]],"date-time":"2002-12-05T03:42:14Z","timestamp":1039059734000},"page":"5695-5701","source":"Crossref","is-referenced-by-count":132,"title":["11\u03b2-Hydroxysteroid Dehydrogenase Types 1 and 2: An Important Pharmacokinetic Determinant for the Activity of Synthetic Mineralo- and Glucocorticoids"],"prefix":"10.1210","volume":"87","author":[{"given":"Sven","family":"Diederich","sequence":"first","affiliation":[{"name":"Department of Endocrinology, Diabetes, and Nutrition, Klinikum Benjamin Franklin, Freie Universita\u0308t Berlin (S.D., E.E., P.B., M.Q., C.B.-V., M.R., W.O., V.B.), 12200 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ekkehard","family":"Eigendorff","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Diabetes, and Nutrition, Klinikum Benjamin Franklin, Freie Universita\u0308t Berlin (S.D., E.E., P.B., M.Q., C.B.-V., M.R., W.O., V.B.), 12200 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Burkhardt","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Diabetes, and Nutrition, Klinikum Benjamin Franklin, Freie Universita\u0308t Berlin (S.D., E.E., P.B., M.Q., C.B.-V., M.R., W.O., V.B.), 12200 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcus","family":"Quinkler","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Diabetes, and Nutrition, Klinikum Benjamin Franklin, Freie Universita\u0308t Berlin (S.D., E.E., P.B., M.Q., C.B.-V., M.R., W.O., V.B.), 12200 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christiane","family":"Bumke-Vogt","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Diabetes, and Nutrition, Klinikum Benjamin Franklin, Freie Universita\u0308t Berlin (S.D., E.E., P.B., M.Q., C.B.-V., M.R., W.O., V.B.), 12200 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Rochel","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Diabetes, and Nutrition, Klinikum Benjamin Franklin, Freie Universita\u0308t Berlin (S.D., E.E., P.B., M.Q., C.B.-V., M.R., W.O., V.B.), 12200 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dieter","family":"Seidelmann","sequence":"additional","affiliation":[{"name":"Research Laboratories of Schering AG (D.S., P. 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