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To assess the hypothesis that cortisol release in rainbow trout is modulated by glucose levels, we first evaluated cortisol release [basal and adrenocorticotropic hormone (ACTH)-regulated] by head kidney tissue superfused with medium reflecting hypoglycaemic, normoglycaemic or hyperglycaemic conditions. Next, cortisol release from head kidney fragments in static incubations was assessed in parallel with changes in parameters related to cortisol synthesis (mRNA abundance of StAR, P450scc, 3βHSD and 11βH) and the GK-mediated glucosensing mechanism (levels of glycogen and glucose, activities of GK, GSase and PK, and mRNA levels of GK, GLUT-2, Kir6.x-like and SUR-like). We then evaluated the effects of two inhibitors of glucose transport, cytochalasin B and phlorizin, on cortisol production and glucosensing mechanisms. The ACTH-induced release of cortisol proved to be modulated by glucose concentration such that increased release occurs under high glucose levels, and decreased ACTH-stimulated cortisol release occurs when glucose transport is inhibited by cytochalasin B. The release of cortisol can be associated with increased synthesis as enhanced mRNA abundance of genes related to cortisol synthesis was also noted in high glucose medium. Specific GK immunoreactivity in the cortisol-producing cells (not in chromaffin cells) further substantiates GK-mediated glucosensing in cortisol production. In contrast, no changes compatible with those of glucose levels and cortisol release/synthesis in the presence of ACTH were noted for any other putative glucosensor mechanisms based on LXR, SGLT-1 or Gnat3. These combined results are the first evidence for a mechanism in fish linking the synthesis and release of a non-pancreatic hormone like cortisol with circulating glucose levels. The relationship was evident for the regulated (ACTH-dependent) pathway and this suggests that under acute stress conditions glucose is important for the regulation of cortisol synthesis and release.

ACTH-stimulated cortisol release from head kidney of rainbow trout is modulated by glucose concentration