| Intracellular glucocorticoid reactivation is catalyzed by 11[beta]-hydroxysteroid dehydrogenase 1 (11[beta]-HSD1), which functions predominantly as a reductase in cells expressing hexose-6-phosphate dehydrogenase (H6PDH). We recently showed that the ratios of cortisone to cortisol and 7-keto- to 7-hydroxy-neurosteroids are regulated by 11[beta]-HSD1 and very much depend on co-expression with H6PDH, providing cosubstrate NADPH. Here, we investigated the impact of H6PDH on the modulation of 11[beta]-HSD1-dependent inter-conversion of cortisone and cortisol by inhibitors and alternative substrates. Using HEK-293 cells expressing 11[beta]-HSD1 or co-expressing 11[beta]-HSD1 and H6PDH, we observed significant differences of 11[beta]-HSD1 inhibition by natural... |
