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It has been established that cortisol plays both mineralocorticoid and glucocorticoid functions by MR and GR, respectively, since the aldosterone hormone is absent. Recently, investigations have proposed that the 11-deoxycorticosterone (DOC) mineralocorticoid precursor might support cortisol effects, but this mechanism remains unclear. Hence, we assessed the early effects of DOC on rainbow trout pre-smolts, the key smoltification stage, via metabolic and transcriptomic approaches. Thirty-six juveniles (~120 g) were treated for 3 h with DOC (1 mg\/kg) and\/or mineralocorticoid (eplerenone) or glucocorticoid (mifepristone) receptor antagonists (n = 6 for each group). DOC decreased plasma glucose and pyruvate and increased phosphate and liver glycogen. DOC also downregulated carbohydrate metabolism-related genes in the liver. Finally, gill RNA-seq analysis presented 1660 differentially expressed transcripts in DOC versus vehicle, 1022 for eplerenone + DOC versus DOC and 3324 for mifepristone + DOC versus DOC. The enrichment analysis mainly revealed the upregulation of ion transmembrane transport and carbohydrate metabolism and the downregulation of stress and innate immune responses. This suggests a significant role of DOC in liver carbohydrate metabolism and gill osmoregulation of pre-smolts through both receptors. Hence, this could contribute to improving animal welfare monitoring during smoltification by featuring novel and potential biomarkers.<\/jats:p>","DOI":"10.3390\/ijms26083725","type":"journal-article","created":{"date-parts":[[2025,4,15]],"date-time":"2025-04-15T06:50:27Z","timestamp":1744699827000},"page":"3725","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Rainbow Trout (Oncorhynchus mykiss) Pre-Smolts Treated with 11-Deoxycorticosterone Regulate Liver Carbohydrate Metabolism and Gill Osmoregulation"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7820-7509","authenticated-orcid":false,"given":"Rodrigo","family":"Zuloaga","sequence":"first","affiliation":[{"name":"Programa de Doctorado en Biotecnolog\u00eda, Facultad de Ciencias de la Vida, Universidad Andres Bello, Santiago 8370186, Chile"},{"name":"Laboratorio de Biotecnolog\u00eda Molecular, Departamento de Ciencias Biol\u00f3gicas, Facultad de Ciencias de la Vida, Universidad Andres Bello, Santiago 8370146, Chile"},{"name":"Interdisciplinary Center for Aquaculture Research (INCAR), Concepci\u00f3n 4030000, Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-6400-3449","authenticated-orcid":false,"given":"Luciano","family":"Ahumada-Langer","sequence":"additional","affiliation":[{"name":"Laboratorio de Biotecnolog\u00eda Molecular, Departamento de Ciencias Biol\u00f3gicas, Facultad de Ciencias de la Vida, Universidad Andres Bello, Santiago 8370146, Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jorge Eduardo","family":"Aedo","sequence":"additional","affiliation":[{"name":"Departamento de Biolog\u00eda y Qu\u00edmica, Facultad de Ciencias B\u00e1sicas, Universidad Cat\u00f3lica del Maule, Talca 3466706, Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-5782-3721","authenticated-orcid":false,"given":"Katalina","family":"Llanos-Az\u00f3car","sequence":"additional","affiliation":[{"name":"Programa de Doctorado en Biotecnolog\u00eda, Facultad de Ciencias de la Vida, Universidad Andres Bello, Santiago 8370186, Chile"},{"name":"Laboratorio de Biotecnolog\u00eda Molecular, Departamento de Ciencias Biol\u00f3gicas, Facultad de Ciencias de la Vida, Universidad Andres Bello, Santiago 8370146, Chile"},{"name":"Interdisciplinary Center for Aquaculture Research (INCAR), Concepci\u00f3n 4030000, Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7411-5391","authenticated-orcid":false,"given":"Alfredo","family":"Molina","sequence":"additional","affiliation":[{"name":"Laboratorio de Biotecnolog\u00eda Molecular, Departamento de Ciencias Biol\u00f3gicas, Facultad de Ciencias de la Vida, Universidad Andres Bello, Santiago 8370146, Chile"},{"name":"Interdisciplinary Center for Aquaculture Research (INCAR), Concepci\u00f3n 4030000, Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan Antonio","family":"Vald\u00e9s","sequence":"additional","affiliation":[{"name":"Laboratorio de Biotecnolog\u00eda Molecular, Departamento de Ciencias Biol\u00f3gicas, Facultad de Ciencias de la Vida, Universidad Andres Bello, Santiago 8370146, Chile"},{"name":"Interdisciplinary Center for Aquaculture Research (INCAR), Concepci\u00f3n 4030000, Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e12993","DOI":"10.1111\/raq.12993","article-title":"Salmon Aquaculture in Chile: Production Growth and Socioeconomic Impacts","volume":"17","author":"Asche","year":"2025","journal-title":"Rev. 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