Characterization of Rapid Nongenomic Cortisol Signalling in Rainbow Trout Liver
Date
2018-08-03
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Abstract
Glucocorticoids are critical in the regulation of metabolic processes for stress adaptation. Cortisol, the primary glucocorticoid in fish, exerts physiological effects through genomic and nongenomic signalling pathways. The genomic response to cortisol is characterized by activation of the corticosteroid receptors, glucocorticoid receptor (GR) and mineralocorticoid receptor (MR), whereas the nongenomic cortisol response involves rapid changes to downstream second-messenger signalling cascades independent of gene regulation. However, nongenomic glucocorticoid signalling remains poorly characterized in teleost models and even more so in the liver, despite the importance of this tissue in regulating both metabolic and physiological adjustments in the face of a stressor. Therefore, the primary objective of this thesis was to further elucidate mechanisms of rapid cortisol signalling in rainbow trout (Oncorhynchus mykiss) liver. The hypothesis tested was that activation of secondary-signalling cascades would mediate rapid cortisol effects and glucocorticoid-membrane receptor(s) were involved in initiating this response. Indeed, stress and the attendant rise in cortisol rapidly modulated cAMP response element binding protein (CREB) phosphorylation, and reduced reactive oxygen species (ROS) generation and glutathione production in vivo. While corticosteroid receptors were identified on the plasma membrane, RU486 had no effect on CREB signalling or ROS generation in vitro, suggesting that these endpoints are GR-independent. Also, cortisol did not rapidly affect the transcript abundance of glucocorticoid-responsive genes associated with the corticosteroid receptors along with biomarkers for immune, growth, metabolic, and oxidative stress systems, suggesting a role for genomic activation in directly regulating the stress response. Furthermore, a membrane-specific cortisol receptor(s) remains unidentified in any species. Altogether, the results presented here propose a role for rapid nongenomic glucocorticoid signalling in modulating the stress-mediated metabolic responses in fish liver, and this provides a novel approach in studying the role of glucocorticoids in mediating stress coping mechanisms.
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Keywords
Glucocorticoids, Nongenomic signalling, metabolism, Stress response, Glucocorticoid receptor, Teleosts, Liver
Citation
Thraya, M. (2018). Characterization of Rapid Nongenomic Cortisol Signalling in Rainbow Trout Liver (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/32790