Corticosterone stimulates pendrin through the intercalated cell mineralocorticoid receptor

Intercalated cell (IC) mineralocorticoid receptor (MR) gene ablation reduces total and apical pendrin, particularly under conditions in which circulating aldosterone concentration is elevated. However, the low or absent 11bHSD2 expression in pendrin-positive ICs should mitigate aldosterone binding to the MR. Therefore, we explored the role of other potential IC MR ligands. We observed that the MR antagonist, spironolactone, reduced pendrin abundance in mice that do not produce aldosterone (aldosterone synthase KO mice). Moreover, 11 b Hydroxysteroid Dehydrogenase 2 (11 b HSD2) gene ablation, which should reduce aldosterone MR receptor binding, paradoxically increased pendrin abundance. We therefore hypothesized that glucocorticoids upregulate pendrin through an IC MR-dependent mechanism. To explore this hypothesis, we examined the effect of glucocorticoids on pendrin abundance and subcellular distribution in wild type mice as well as in floxed and IC MR knockout mice. We observed that corticosterone increased total and apical pendrin abundance in adrenalectomized mice, although dexamethasone at comparable doses was without effect. Moreover, pendrin abundance was lower in adrenalectomized, corticosterone-treated ICs MR KO than in floxed MR controls. We conclude that glucocorticoids act through an IC MR-dependent mechanism to upregulate pendrin. DK110375 (to ED and SMW) and DK 119793 (to SMW) This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.