Stirring Up New Ideas About the Regulation of the Hypothalamic-Pituitary-Interrenal Axis in Zebrafish (Danio rerio)

The dynamic relationships between the changes in cortisol synthesis during and after a stressor and the expression pattern of the key genes that regulate the different levels of the hypothalamic-pituitary-interrenal (HPI) stress axis are poorly understood. This study established a novel vortex stressor and characterized its impact at all levels of the HPI axis in adult zebrafish. Exposure to a moderate vortex speed for 60 min was associated with a marked 18-fold increase in whole-body cortisol after 10 min followed by a gradual return to basal values 30 min poststress. The changes in whole-body cortisol were paralleled by increases in the expression of preoptic area corticotropin-releasing factor, pituitary prohormone convertase 1, and interrenal melanocortin 2 receptor, steroid acute regulatory protein, 11β-hydroxylase and 11β-hydroxysteroid dehydrogenase 2. The response to the vortex stressor also included delayed increases in preoptic area urotensin I and pituitary pro-opiomelanocortin mRNA levels but no change in the expression of other putative HPI axis regulators. Notably, the expression of several genes was depressed below control values 30 min poststress. These findings suggest that multiple genes at all levels of the HPI axis play an active role in the stimulation and termination of the cortisol stress response in zebrafish.