{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T17:52:48Z","timestamp":1787161968702,"version":"build-2736575974"},"reference-count":42,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2024,1,6]],"date-time":"2024-01-06T00:00:00Z","timestamp":1704499200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Katjes Fassin GmbH &amp; Co. KG"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Aldosterone (Aldo) exerts its action through binding with the mineralocorticoid receptor (MR). Clinically, a link between primary aldosteronism (PA) and thyroid diseases has been hypothesised. However, the presence and activity of MR on the thyroid have not yet been demonstrated. We investigated the gene\/protein expression and activation of MR in primary thyroid cell cultures (normal rat thyroid [FRTL-5] and human papillary thyroid cancer [PTC] cell lines, BCPAP and K1) through qRT-PCR analysis, immunofluorescence, and confocal microscopy. We also studied the effects of Aldo on thyroid-specific and inflammation genes in vitro. Paired human normal and neoplastic thyroid tissues were also studied. We demonstrated both gene and protein expression and activation of MR in normal rat thyroid and human PTC lines. Incubation with Aldo induced an acute increase in IL-6 expression in both the FRTL-5 and BCPAP lines, which was antagonised by spironolactone, and an acute and late upregulation of thyroid-specific genes in FRTL-5. MR was also expressed at both gene and protein levels in normal human thyroid tissues and in PTC, with a progressive decline during neoplastic tumourigenesis, particularly in more aggressive histotypes. We present the first evidence of MR gene and protein expression in both normal and pathological thyroid cells and tissues. We have shown that MR is present and functionally activated in thyroid tissue. Binding of Aldo to MR induces the expression of inflammatory and thyroid-specific genes, and the thyroid may thus be considered a novel mineralocorticoid target tissue.<\/jats:p>","DOI":"10.3390\/ijms25020754","type":"journal-article","created":{"date-parts":[[2024,1,8]],"date-time":"2024-01-08T07:59:20Z","timestamp":1704700760000},"page":"754","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["First Evidence of Mineralocorticoid Receptor Gene and Protein Expression in Rat and Human Thyroid Tissues and Cell Cultures"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2403-4339","authenticated-orcid":false,"given":"Jacopo","family":"Manso","sequence":"first","affiliation":[{"name":"Endocrinology Unit, Department of Medicine (DIMED), University of Padua, Via Ospedale Civile 105, 35128 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Chiara","family":"Pedron","sequence":"additional","affiliation":[{"name":"Endocrinology Unit, Department of Medicine (DIMED), University of Padua, Via Ospedale Civile 105, 35128 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1182-8324","authenticated-orcid":false,"given":"Alberto","family":"Mondin","sequence":"additional","affiliation":[{"name":"Endocrinology Unit, Department of Medicine (DIMED), University of Padua, Via Ospedale Civile 105, 35128 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6946-9673","authenticated-orcid":false,"given":"Simona","family":"Censi","sequence":"additional","affiliation":[{"name":"Endocrinology Unit, Department of Medicine (DIMED), University of Padua, Via Ospedale Civile 105, 35128 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianmaria","family":"Pennelli","sequence":"additional","affiliation":[{"name":"Surgical Pathology Unit, Department of Medicine (DIMED), University of Padua, Via Ospedale Civile 105, 35128 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3245-2322","authenticated-orcid":false,"given":"Francesca","family":"Galuppini","sequence":"additional","affiliation":[{"name":"Surgical Pathology Unit, Department of Medicine (DIMED), University of Padua, Via Ospedale Civile 105, 35128 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5821-2693","authenticated-orcid":false,"given":"Susi","family":"Barollo","sequence":"additional","affiliation":[{"name":"Endocrinology Unit, Department of Medicine (DIMED), University of Padua, Via Ospedale Civile 105, 35128 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7931-0084","authenticated-orcid":false,"given":"Loris","family":"Bertazza","sequence":"additional","affiliation":[{"name":"Endocrinology Unit, Department of Medicine (DIMED), University of Padua, Via Ospedale Civile 105, 35128 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5548-9785","authenticated-orcid":false,"given":"Claudia Maria","family":"Radu","sequence":"additional","affiliation":[{"name":"General Internal Medicine and Thrombotic and Haemorrhagic Diseases Unit, Department of Medicine (DIMED), University of Padua, Via Ospedale Civile 105, 35128 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Ghini","sequence":"additional","affiliation":[{"name":"Endocrinology Unit, Department of Medicine (DIMED), University of Padua, Via Ospedale Civile 105, 35128 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6744-383X","authenticated-orcid":false,"given":"Paolo","family":"Simioni","sequence":"additional","affiliation":[{"name":"General Internal Medicine and Thrombotic and Haemorrhagic Diseases Unit, Department of Medicine (DIMED), University of Padua, Via Ospedale Civile 105, 35128 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1526-6832","authenticated-orcid":false,"given":"Chiara","family":"Sabbadin","sequence":"additional","affiliation":[{"name":"Endocrinology Unit, Department of Medicine (DIMED), University of Padua, Via Ospedale Civile 105, 35128 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1456-8716","authenticated-orcid":false,"given":"Filippo","family":"Ceccato","sequence":"additional","affiliation":[{"name":"Endocrinology Unit, Department of Medicine (DIMED), University of Padua, Via Ospedale Civile 105, 35128 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6433-5155","authenticated-orcid":false,"given":"Decio","family":"Armanini","sequence":"additional","affiliation":[{"name":"Endocrinology Unit, Department of Medicine (DIMED), University of Padua, Via Ospedale Civile 105, 35128 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2615-8001","authenticated-orcid":false,"given":"Caterina","family":"Mian","sequence":"additional","affiliation":[{"name":"Endocrinology Unit, Department of Medicine (DIMED), University of Padua, Via Ospedale Civile 105, 35128 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1530\/eje.1.02330","article-title":"Functional characterization of naturally occurring NR3C2 gene mutations in Italian patients suffering from pseudohypoaldosteronism type 1","volume":"156","author":"Balsamo","year":"2007","journal-title":"Eur. J. Endocrinol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1152\/advan.00051.2001","article-title":"Aldosterone","volume":"26","author":"Booth","year":"2002","journal-title":"Adv. Physiol. Educ."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1877","DOI":"10.1210\/mend-3-11-1877","article-title":"Molecular cloning of a mineralocorticoid (type I) receptor complementary DNA from rat hippocampus","volume":"3","author":"Patel","year":"1989","journal-title":"Mol. Endocrinol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1111\/j.1440-1681.1987.tb02422.x","article-title":"High affinity aldosterone binding sites (type I receptors) in rat heart","volume":"14","author":"Pearce","year":"1987","journal-title":"Clin. Exp. Pharmacol. Physiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1126\/science.2845584","article-title":"Mineralocorticoid action: Target tissue specificity is enzyme, not receptor, mediated","volume":"242","author":"Funder","year":"1988","journal-title":"Science"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1359","DOI":"10.1161\/CIRCRESAHA.108.174235","article-title":"Functional mineralocorticoid receptors in human vascular endothelial cells regulate intercellular adhesion molecule-1 expression and promote leukocyte adhesion","volume":"102","author":"Caprio","year":"2008","journal-title":"Circ. Res."},{"key":"ref_7","first-page":"479","article-title":"Parallel determination of mineralocorticoid and glucocorticoid receptors in T- and B-lymphocytes of human spleen","volume":"118","author":"Armanini","year":"1988","journal-title":"Acta Endocrinol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"E386","DOI":"10.1152\/ajpendo.2000.279.2.E386","article-title":"The mineralocorticoid receptor mediates aldosterone-induced differentiation of T37i cells into brown adipocytes","volume":"279","author":"Penfornis","year":"2000","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2185","DOI":"10.1096\/fj.06-7970com","article-title":"Pivotal role of the mineralocorticoid receptor in corticosteroid-induced adipogenesis","volume":"21","author":"Caprio","year":"2007","journal-title":"FASEB J."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2494","DOI":"10.1210\/jc.2012-3571","article-title":"Human red blood cells alterations in primary aldosteronism","volume":"98","author":"Bordin","year":"2013","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1661","DOI":"10.1007\/s00424-013-1282-4","article-title":"Smooth muscle cell mineralocorticoid receptors: Role in vascular function and contribution to cardiovascular disease","volume":"465","author":"McCurley","year":"2013","journal-title":"Pflug. Arch."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1973","DOI":"10.1210\/jc.2003-031545","article-title":"Effect of aldosterone and glycyrrhetinic acid on the protein expression of PAI-1 and p22(phox) in human mononuclear leukocytes","volume":"89","author":"Calo","year":"2004","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.steroids.2014.04.005","article-title":"Mineralocorticoid receptors in immune cells: Emerging role in cardiovascular disease","volume":"91","author":"Bene","year":"2014","journal-title":"Steroids"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1007\/BF03346533","article-title":"Primary aldosteronism can alter peripheral levels of transforming growth factor beta and tumor necrosis factor alpha","volume":"32","author":"Carvajal","year":"2009","journal-title":"J. Endocrinol. Invest."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"191","DOI":"10.4049\/jimmunol.0802886","article-title":"Aldosterone promotes autoimmune damage by enhancing Th17-mediated immunity","volume":"184","author":"Herrada","year":"2010","journal-title":"J. Immunol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1016\/j.tem.2014.09.001","article-title":"Hashimoto\u2019s thyroiditis and papillary thyroid cancer: Are they immunologically linked?","volume":"25","author":"Ehlers","year":"2014","journal-title":"Trends. Endocrinol. Metab."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"3908061","DOI":"10.1155\/2017\/3908061","article-title":"The Role of IL-17 and Related Cytokines in Inflammatory Autoimmune Diseases","volume":"2017","author":"Kuwabara","year":"2017","journal-title":"Mediat. Inflamm."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1007\/s12020-016-0880-2","article-title":"Association of primary aldosteronism with chronic thyroiditis","volume":"55","author":"Sabbadin","year":"2017","journal-title":"Endocrine"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1385\/ENDO:22:2:155","article-title":"High prevalence of thyroid ultrasonographic abnormalities in primary aldosteronism","volume":"22","author":"Armanini","year":"2003","journal-title":"Endocrine"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2561","DOI":"10.1007\/s00296-011-2032-6","article-title":"Coexistence of primary aldosteronism and Hashimoto\u2019s thyroiditis","volume":"32","author":"Krysiak","year":"2012","journal-title":"Rheumatol. Int."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1124\/pr.115.011106","article-title":"Emerging Roles of the Mineralocorticoid Receptor in Pathology: Toward New Paradigms in Clinical Pharmacology","volume":"68","author":"Jaisser","year":"2016","journal-title":"Pharmacol. Rev."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1016\/j.kint.2019.02.030","article-title":"Mineralocorticoid receptor antagonists and kidney diseases: Pathophysiological basis","volume":"96","author":"Girerd","year":"2019","journal-title":"Kidney Int."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"T125","DOI":"10.1530\/JOE-16-0600","article-title":"30 Years of the Mineralocorticoid Receptor: Mineralocorticoid receptor antagonists: 60 years of research and development","volume":"234","author":"Kolkhof","year":"2017","journal-title":"J. Endocrinol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3305","DOI":"10.1210\/endo-129-6-3305","article-title":"11 beta-hydroxysteroid dehydrogenase in vascular smooth muscle and heart: Implications for cardiovascular responses to glucocorticoids","volume":"129","author":"Walker","year":"1991","journal-title":"Endocrinology"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/0960-0760(92)90220-D","article-title":"Tissue localization of 11 beta-hydroxysteroid dehydrogenase and its relationship to the glucocorticoid receptor","volume":"41","author":"Whorwood","year":"1992","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"R1","DOI":"10.1530\/JME-16-0128","article-title":"Getting to the heart of intracellular glucocorticoid regeneration: 11beta-HSD1 in the myocardium","volume":"58","author":"Gray","year":"2017","journal-title":"J. Mol. Endocrinol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1309","DOI":"10.1056\/NEJMoa030207","article-title":"Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction","volume":"348","author":"Pitt","year":"2003","journal-title":"N. Engl. J. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"882330","DOI":"10.3389\/fcvm.2022.882330","article-title":"Primary Aldosteronism and Ischemic Heart Disease","volume":"9","author":"Patil","year":"2022","journal-title":"Front. Cardiovasc. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1186\/s12935-022-02680-1","article-title":"Evolution of intra-tumoral heterogeneity across different pathological stages in papillary thyroid carcinoma","volume":"22","author":"Affinito","year":"2022","journal-title":"Cancer Cell Int."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"133","DOI":"10.3389\/fendo.2012.00133","article-title":"Thyroid cancer cell lines: An overview","volume":"3","author":"Saiselet","year":"2012","journal-title":"Front. Endocrinol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1146\/annurev-physiol-060821-013950","article-title":"Roles of Mineralocorticoid Receptors in Cardiovascular and Cardiorenal Diseases","volume":"84","author":"Bonnard","year":"2022","journal-title":"Annu. Rev. Physiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1274","DOI":"10.1038\/ajh.2011.144","article-title":"Blood pressure, thyroid-stimulating hormone, and thyroid disease prevalence in primary aldosteronism and essential hypertension","volume":"24","author":"Turchi","year":"2011","journal-title":"Am. J. Hypertens"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1152\/physiolgenomics.00084.2017","article-title":"RNA sequencing of kidney distal tubule cells reveals multiple mediators of chronic aldosterone action","volume":"50","author":"Poulsen","year":"2018","journal-title":"Physiol. Genom."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1161\/01.HYP.0000088321.67254.B7","article-title":"Deoxycorticosterone upregulates PDS (Slc26a4) in mouse kidney: Role of pendrin in mineralocorticoid-induced hypertension","volume":"42","author":"Verlander","year":"2003","journal-title":"Hypertension"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1507\/endocrj1954.28.735","article-title":"Primary aldosteronism associated with a primary double cancer of the thyroid and rectum: Report of a case","volume":"28","author":"Nishikawa","year":"1981","journal-title":"Endocrinol. Jpn."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e45","DOI":"10.4081\/rt.2011.e45","article-title":"A rare case of an aldosterone secreting metastatic adrenocortical carcinoma and papillary thyroid carcinoma in a 31-year-old male","volume":"3","author":"Wanta","year":"2011","journal-title":"Rare Tumors"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"497","DOI":"10.2169\/internalmedicine.0891-18","article-title":"Association of Papillary Thyroid Carcinoma with Primary Aldosteronism","volume":"58","author":"Nakamura","year":"2019","journal-title":"Intern. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1182","DOI":"10.5966\/sctm.2014-0090","article-title":"Concise review: Dedifferentiation meets cancer development: Proof of concept for epigenetic cancer","volume":"3","author":"Yamada","year":"2014","journal-title":"Stem. Cells Transl. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"647369","DOI":"10.3389\/fendo.2021.647369","article-title":"Serum miR-375 for Diagnostic and Prognostic Purposes in Medullary Thyroid Carcinoma","volume":"12","author":"Censi","year":"2021","journal-title":"Front. Endocrinol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1161\/01.HYP.0000182661.98259.4f","article-title":"Nongenomic effects of aldosterone in the human heart: Interaction with angiotensin II","volume":"46","author":"Chai","year":"2005","journal-title":"Hypertension"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"912","DOI":"10.1111\/j.1440-1681.2010.05405.x","article-title":"Celecoxib, but not rofecoxib or naproxen, attenuates cardiac hypertrophy and fibrosis induced in vitro by angiotensin and aldosterone","volume":"37","author":"Wang","year":"2010","journal-title":"Clin. Exp. Pharmacol. Physiol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1160384","DOI":"10.3389\/fvets.2023.1160384","article-title":"Identification of stable reference genes for quantitative gene expression analysis in the duodenum of meat-type ducks","volume":"10","author":"Shui","year":"2023","journal-title":"Front. Vet. Sci."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/2\/754\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T13:41:27Z","timestamp":1760103687000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/2\/754"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,6]]},"references-count":42,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2024,1]]}},"alternative-id":["ijms25020754"],"URL":"https:\/\/doi.org\/10.3390\/ijms25020754","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1,6]]}}}