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Aldosterone modulates hormone receptor binding to unique elements in the endothelin‐1 (ET‐1) promoter
Author(s) -
Stow Lisa R,
Gumz Michelle L,
Lynch I Jeanette,
Greenlee Megan M,
Cain Brian D,
Wingo Charles S
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.1014.3
Subject(s) - aldosterone , mineralocorticoid receptor , medicine , endocrinology , mineralocorticoid , receptor , biology , glucocorticoid receptor , in vivo , hormone , chemistry , glucocorticoid , microbiology and biotechnology
We previously identified ET‐1 as an aldosterone‐induced gene in inner medullary collecting duct (IMCD) cells. These hormones exert opposing action on renal sodium transport, and this interaction may represent the first known negative feedback loop on renal aldosterone signaling. In these studies we verified the interaction in rat; aldosterone stimulated ET‐1 mRNA in IMCD ex vivo and ET‐1 peptide in inner medulla in vivo . We mapped 2 unique hormone response elements (HREs) in the ET‐1 promoter and confirmed mRNA stimulation occurred by transcription. RNA silencing corroborated pharmacological data and showed aldosterone utilized both mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) in this response. Notably, ET‐1 mRNA stimulated by a small physiological aldosterone dose (10 nM) was accompanied by nuclear translocation and direct binding of MR and GR to ET‐1 HREs. Aldosterone, but not competitive inhibitors, recruited coactivators, modified histones and RNA polymerase II to the ET‐1 promoter. In summary, aldosterone action on ET‐1 occurs in vivo , involves novel MR/GR cooperation at unique HREs, and may mediate crucial negative feedback on aldosterone action. Supported by NIDDK and AHA.