11 beta-hydroxysteroid dehydrogenase activity in human lung cells and transcription regulation by glucocorticoids.
Selectivity to aldosterone (Aldo) in mineralocorticoid target tissues has been suggested to be due to the activity of 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD). This enzyme inactivates the endogenous glucocorticoid cortisol, thus permitting the unhindered access of Aldo to the mineralocorticoid receptor. The 11 beta-HSD activity was measured by the conversion of cortisol to cortisone and vice versa. Concomitant treatment of the cells with either cortisone or cortisol in the presence of the glycyrrhetinic acid derivative carbenoxolone (CBX) blocked both activities of 11 beta-HSD. Dexamethasone and Aldo activated the transcription of transiently transfected mouse mammary tumor virus-bacterial chloramphenicol acetyltransferase chimeric gene in LU-19 cells. The transcription activation by cortisol was synergized by concomitant treatment of the transfectants with CBX. Transactivation with Aldo was inhibited by spironolactone. The enzyme 11 beta-HSD in LU-19 cells is similar to the cloned liver isoform and catalyzes both reduction and dehydrogenation.
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Medical Research Council Group in Molecular Endocrinology, Laval University Medical Center, Quebec, Canada.
Warriar
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Govindan
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D042842:11-beta-Hydroxysteroid Dehydrogenases; D000328:Adult; D000345:Affinity Labels; D000906:Antibodies / Q000276:immunology; D002460:Cell Line; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology*; D006433:Hemocyanins / Q000276:immunology; D006801:Humans; D006854:Hydrocortisone / Q000037:antagonists & inhibitors; D006913:Hydroxysteroid Dehydrogenases / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*; D008168:Lung / Q000166:cytology / Q000201:enzymology*; D010088:Oxidoreductases / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D011987:Receptors, Steroid / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects*; D015533:Transcriptional Activation; D014466:Ultraviolet Rays
D000345:Affinity Labels; D000906:Antibodies; D005938:Glucocorticoids; D011965:Receptors, Glucocorticoid; D011987:Receptors, Steroid; D006433:Hemocyanins; D010088:Oxidoreductases; D006913:Hydroxysteroid Dehydrogenases; D042842:11-beta-Hydroxysteroid Dehydrogenases; C032808:keyhole-limpet hemocyanin; D006854:Hydrocortisone