biostudies-literaturePham TDHHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)NIDDK NIH HHSF144-F157https://www.ebi.ac.uk/biostudies/studies/S-EPMC12867009biostudies-literatureUnknown330(2)NaCl restriction upregulates pendrin, in part, through increased circulating aldosterone and the intercalated cell (IC) mineralocorticoid receptor (MR). Since 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) enhances aldosterone binding to this receptor in other cells, we asked if pendrin abundance is reduced in NaCl-restricted 11β-HSD2 knockout (KO) rats. However, pendrin abundance was greater in 11β-HSD2 KOs than in controls, possibly from enhanced glucocorticoid MR activation. Moreover, the MR antagonist, spironolactone, reduced pendrin abundance in mice that do not produce aldosterone (aldosterone synthase KO). IC MR gene ablation also reduced pendrin protein abundance in corticosterone-treated, adrenalectomized mice. Therefore, the MR regulates pendrin independently of aldosterone. American journal of physiology. Renal physiologyPendrin is upregulated by corticosterone and participates in its pressor response.PMC12867009R01 DK123180DK10375DK123180K08 DK120873R01 DK110375R01 DK119793DK 10375DK 120873Castro RALuther JMSurendran KMullins LJHarris ANMullins JJWall SMFerdaus MZDelpire ESimmons APham TDAbood DCfalsePendrin is upregulated by corticosterone and participates in its pressor response.NaCl restriction upregulates pendrin, in part, through increased circulating aldosterone and the intercalated cell (IC) mineralocorticoid receptor (MR). Since 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) enhances aldosterone binding to this receptor in other cells, we asked if pendrin abundance is reduced in NaCl-restricted 11β-HSD2 knockout (KO) rats. However, pendrin abundance was greater in 11β-HSD2 KOs than in controls, possibly from enhanced glucocorticoid MR activation. Moreover, the MR antagonist, spironolactone, reduced pendrin abundance in mice that do not produce aldosterone (aldosterone synthase KO). IC MR gene ablation also reduced pendrin protein abundance in corticosterone-treated, adrenalectomized mice. Therefore, the MR regulates pendrin independently of aldosterone. 2026-01-01T00:00:00Z2026 Feb2026-06-27T03:11:46.627Z2026-06-27T03:05:57.458ZS-EPMC128670094145260210.1152/ajprenal.00194.2025