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• W2004235040 abstract "11β-Hydroxysteroid dehydrogenase (11βHSD) converts endogenous glucocorticoids to their biologically inactive 11-dehydro derivatives and is therefore able to determine, at least in part, the biological action of glucocorticoids. Type 1 11βHSD has both oxidase and reductase activities interconverting corticosterone and 11-dehydrocorticosterone, whereas type 2 11βHSD has only oxidase activity converting corticosterone to 11-dehydrocorticosterone. Since 11βHSD expression is regulated during development and by hormones in a tissue-specific manner and since glucocorticoids play an important role in postnatal intestinal maturation, we investigated the role of corticosteroids and cytodifferentiation in the regulation of intestinal 11βHSD. Using rat intestinal organ cultures and epithelial cell lines derived from rat small intestine (IEC-6, IEC-18) and from human colon adenocarcinoma (Caco-2, HT-29), we analyzed the effect of corticosteroids and cytodifferentiation on 11βHSD. Screening of the clonal cell lines showed that Caco-2 cells expressed by far the greatest 11βHSD2 oxidase activity, lower activity was observed in HT-29 cells, and lowest activity was seen in IEC cells. Treatment with dexamethasone (50 nM) increased the activity of 11βHSD2 in IEC-6 cells (+59%) and HT-29 cells (+31%), whereas aldosterone (50 nM) stimulated 11βHSD2 in IEC-6 cells only (+31%). Caco-2 cells and IEC-18 cells did not respond to corticosteroids. Growth of IEC-6 cells on Matrigel, treatment of HT-29 cells with butyrate, and postconfluency of Caco-2 cells increased not only the markers of cytodifferentiation, such as alkaline phosphatase and sucrase, but also the activity of 11βHSD2 in all of these cell lines (IEC-6, +96%; HT-29, +139%; Caco-2, +95%). Addition of corticosteroids to these more differentiated cell cultures did not enhance 11βHSD2 activity. In intestinal organ cultures of suckling rat small intestine, dexamethasone and aldosterone stimulated 11βHSD by more than 300%. We conclude that corticosteroids markedly and differentially regulate intestinal 11βHSD2 and that cytodifferentiation of intestinal epithelial cells is associated with upregulation of 11βHSD2 activity that is independent of corticosteroids." @default.
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• W2004235040 date "2002-02-01" @default.
• W2004235040 modified "2023-10-13" @default.
• W2004235040 title "Effect of cellular differentiation on 11β-hydroxysteroid dehydrogenase activity in the intestine" @default.
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• W2004235040 doi "https://doi.org/10.1016/s0039-128x(01)00143-x" @default.
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