Figure 7.

In the absence of aldosterone, glucocorticoids stimulate the epithelial Na⁺ channel (ENaC) in the late distal convoluted tubule (DCT2)/connecting tubule (CNT) but not in the CNT/cortical collecting duct (CCD). Low expression of 11β-hydroxysteroid dehydrogenase 2 (11β-HSD2) in the DCT2/CNT probably allows glucocorticoids to stimulate mineralocorticoid receptor (MR), resulting in aldosterone-independent ENaC activity in this nephron segment. Shown is a schematic diagram of a distal tubule with the early distal convoluted tubule (DCT1), DCT2, CNT, and CCD. The convergence of two CNTs marks the beginning of the CCD. The expression pattern of 11β-HSD2, MR, and apically localized ENaC is illustrated in green, red, and blue, respectively, with color intensity reflecting the level of expression. MR-mediated ENaC activation (red arrows) can only occur in those parts of the nephron where 11β-HSD2 does not prevent (X) glucocorticoid action (black arrows). Please note that the diagram corresponds to a situation in which the circulating aldosterone level is negligible and apical ENaC expression is essentially absent in the late CNT and CCD where ENaC activity is known to be aldosterone dependent (6).