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Aldosterone plays vital physiological roles through the mineralocorticoid receptor (MR) but in certain cell types, it can also activate the glucocorticoid (GC) receptor (GR). Both MR and GR are structurally and functionally related and belong to the same family of ligand-dependent transcription factors that recognize identical GC regulatory elements (GREs) on their target genes. GCs play key roles in skin pathophysiology acting through both GR and MR; however, the effects of aldosterone and the potential association of PA and skin disease were not previously addressed. Skin samples from PA revealed histopathological alterations relative to control subjects, featuring epidermal hyperplasia, impaired differentiation, and increased dermal infiltrates, correlating with increased NF-\u03baB signaling and up-regulation of TNF-A and IL-6 cytokines. PA skin samples also showed significantly higher expression of MR, GR, and HSD11B2. In cultured keratinocytes, aldosterone treatment increased GRE transcriptional activity which was significantly inhibited by co-treatment with GR- and MR-antagonists. This study demonstrates that high levels of aldosterone in PA patients correlate with skin anomalies and inflammatory features associated with abnormal GR\/MR activation in epidermal keratinocytes.<\/jats:p>","DOI":"10.1038\/s41598-017-16216-5","type":"journal-article","created":{"date-parts":[[2017,11,13]],"date-time":"2017-11-13T09:21:47Z","timestamp":1510564907000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Primary aldosteronism patients show skin alterations and abnormal activation of glucocorticoid receptor in keratinocytes"],"prefix":"10.1038","volume":"7","author":[{"given":"Julia","family":"Boix","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judit","family":"Bigas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa M.","family":"Sevilla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maurizio","family":"Iacobone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marilisa","family":"Citton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Torresan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brasilina","family":"Caroccia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7963-0931","authenticated-orcid":false,"given":"Gian Paolo","family":"Rossi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7166-2824","authenticated-orcid":false,"given":"Paloma","family":"P\u00e9rez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,11,17]]},"reference":[{"key":"16216_CR1","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1016\/j.coph.2014.12.005","volume":"21","author":"L Lenzini","year":"2015","unstructured":"Lenzini, L. & Rossi, G. 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