Regulation and function of the gill corticotropin-releasing factor system during osmoregulatory disturbances in Atlantic salmon

While corticosteroids, including cortisol, have conserved osmoregulatory functions, the relative involvement of other stress-related hormones in osmoregulatory processes remains unclear. To address this gap, we initially characterized the gill corticotropin-releasing factor (CRF) system of Atlantic salmon (Salmo salar) and then determined: 1) how it is influenced by osmotic disturbances; 2) whether it is affected by cortisol; and 3) which physiological processes it regulates in the gills. Most CRF system components were expressed in the gills with CRF receptor 2 (crfr2a), CRF binding protein (crfbp1 and crfbp2), and urocortin 2 (ucn2a) being the most abundant. The development of seawater tolerance in migratory juveniles (i.e., smolts) was associated with a general transcriptional upregulation of CRF ligands, but transcript levels of crfr2a, crfbp2, crfb2, and ucn2a decreased by ∼50% following seawater transfer. Accordingly, transfer of seawater-acclimated fish into freshwater increased crfr2a and ucn2a levels. Cortisol treatment of cultured gill filaments had marked effects on the CRF system; however, these effects failed to fully replicate changes observed during in vivo experiments, suggesting direct contributions of the gill CRF system during osmotic disturbances. Indeed, activation of the CRF system in cultured filaments from freshwater-acclimated (but not seawater-acclimated) salmon had transcriptional effects on several physiological systems (e.g., endothelial permeability, angiogenesis, and immune regulation) which involved contributions by both CRF receptor subtypes. Overall, our results indicate that the gill CRF system is more active in hypoosmotic environments and directly contributes to the coordination of physiological responses following osmotic disturbances.