Zuloaga Rodrigo, Ahumada-Langer Luciano, Aedo Jorge Eduardo, Llanos-Azócar Katalina, Molina Alfredo, Valdés Juan Antonio
Programa de Doctorado en Biotecnología, Facultad de Ciencias de la Vida, Universidad Andres Bello, Santiago 8370186, Chile.
Laboratorio de Biotecnología Molecular, Departamento de Ciencias Biológicas, Facultad de Ciencias de la Vida, Universidad Andres Bello, Santiago 8370146, Chile.
Int J Mol Sci. 2025 Apr 15;26(8):3725. doi: 10.3390/ijms26083725.
Smoltification is stressful for salmonids, and cortisol is one of the central endocrine regulators for seawater adaptation. 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 ( = 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.
银化对鲑科鱼类来说是有压力的，而皮质醇是海水适应过程中的核心内分泌调节因子之一。由于缺乏醛固酮激素，皮质醇已被证实分别通过盐皮质激素受体（MR）和糖皮质激素受体（GR）发挥盐皮质激素和糖皮质激素的功能。最近，有研究提出11-脱氧皮质酮（DOC）这种盐皮质激素前体可能支持皮质醇的作用，但该机制仍不清楚。因此，我们通过代谢和转录组学方法评估了DOC对虹鳟鱼幼鱼（银化关键阶段）的早期影响。36尾幼鱼（约120克）用DOC（1毫克/千克）和/或盐皮质激素（依普利酮）或糖皮质激素（米非司酮）受体拮抗剂处理3小时（每组6尾）。DOC降低了血浆葡萄糖和丙酮酸水平，增加了磷酸盐和肝糖原含量。DOC还下调了肝脏中与碳水化合物代谢相关的基因。最后，鳃RNA测序分析显示，DOC处理组与对照组相比有1660个差异表达转录本，依普利酮+DOC处理组与DOC处理组相比有1022个，米非司酮+DOC处理组与DOC处理组相比有3324个。富集分析主要揭示了离子跨膜运输和碳水化合物代谢的上调以及应激和先天免疫反应的下调。这表明DOC通过两种受体在幼鱼的肝脏碳水化合物代谢和鳃渗透调节中发挥重要作用。因此，这可能有助于通过发现新的潜在生物标志物来改善银化过程中的动物福利监测。
