LeBlanc S, Höglund E, Gilmour KM, Currie S. Hormonal modulation of the heat shock response: insights from fish with divergent cortisol stress responses. Am J Physiol Regul Integr Comp Physiol 302: R184-R192, 2012. First published October 26, 2011 doi:10.1152/ajpregu.00196.2011.-Acute temperature stress in animals results in increases in heat shock proteins (HSPs) and stress hormones. There is evidence that stress hormones influence the magnitude of the heat shock response; however, their role is equivocal. To determine whether and how stress hormones may affect the heat shock response, we capitalized on two lines of rainbow trout specifically bred for their high (HR) and low (LR) cortisol response to stress. We predicted that LR fish, with a low cortisol but high catecholamine response to stress, would induce higher levels of HSPs after acute heat stress than HR trout. We found that HR fish have significantly higher increases in both catecholamines and cortisol compared with LR fish, and LR fish had no appreciable stress hormone response to heat shock. This unexpected finding prevented further interpretation of the hormonal modulation of the heat shock response but provided insight into stress-coping styles and environmental stress. HR fish also had a significantly greater and faster heat shock response and less oxidative protein damage than LR fish. Despite these clear differences in the physiological and cellular responses to heat shock, there were no differences in the thermal tolerance of HR and LR fish. Our results support the hypothesis that responsiveness to environmental change underpins the physiological differences in stress-coping styles. Here, we demonstrate that the heat shock response is a distinguishing feature of the HR and LR lines and suggest that it may have been coselected with the hormonal responses to stress. heat shock protein; catecholamines; heat stress; thermal tolerance; high-responding; low-responding HEAT SHOCK PROTEINS (HSPs) are molecular chaperones responsible for the repair of damaged proteins and assist in folding of new proteins. They increase following cellular stress resulting from exposure to high temperature, ischemia-reperfusion, or oxidative damage, and they have been found in every organism in which they have been sought (13, 21). The putative trigger for HSP induction is an increase in damaged proteins within the cell (1), which frees the heat shock transcription factor (e.g., HSF1) to initiate rapid increases in gene transcription followed by translation into HSPs (31). Although an increase in damaged proteins is likely the primary trigger for HSP induction following stress; stress hormones, including catecholamines and cortisol, influence transcription and translation of HSP genes and proteins. Catecholamines appear to augment stress-induced HSP gene transcripts and proteins in mammals (32, 39, 54), fish (9), and invertebrates (23). The glucocorticoid receptor is chaperoned by several HSPs, mainly the HSP90 and HSP70 families (17), so it is perhaps not surprising tha...