4 - The Molecular Stress Response

Abstract

1. Introduction 2. Molecular Regulation of the Hypothalamic–Pituitary–Interrenal (HPI) Axis 2.1. Hypothalamus 2.2. Pituitary 2.3. Head Kidney (Interrenal Tissue) 3. Genomic Cortisol Signaling 3.1. Glucocorticoid Receptor 3.2. Mineralocorticoid Receptor 4. Genomic Effects of Cortisol 4.1. Development of the Stress Axis 4.2. Molecular Adjustments During Stress 4.3. Cellular Adjustments 5. Significance of Molecular Responses 6. Approaches to Study Molecular Responses to Stress 6.1. Mechanistic Studies Using Targeted Mutagenesis 6.2. Epigenetic Regulation of Stress Response 7. Concluding Remarks and the Unknowns In this chapter we summarize the key patterns observed in the transcript abundances of genes involved in the hypothalamic–pituitary–interrenal (HPI) axis regulation, as well as regulation of stress-responsive genes that are modulated by corticosteroid signaling in fish. Plasma levels of cortisol, the primary corticosteroid in teleosts, rise within minutes after a stressor encounter, and this steroid action is mediated primarily by genomic signaling involving the family of nuclear receptors including the glucocorticoid receptor (GR) and mineralocorticoid receptor (MR). Specific molecular responses in target tissues associated with activation of these corticosteroid receptors have become apparent by increased use of receptor antagonists and gene knockdown tools. Although molecular adjustments to stress are dependent on species, developmental stage, type, and duration of stressor, overall cortisol action limits energy-demanding processes and enhances energy mobilization and reallocation. Recent work has also underscored the necessity of maternal cortisol and GR signaling as essential for fish development, but the underlying mechanisms are far from clear. While transcript abundance is an excellent indicator of pathway modulation by cortisol, this data by itself lacks physiological relevance unless accompanied by downstream protein and/or metabolite changes. As the field of molecular biology continues to advance, approaches including next-generation sequencing and gene editing tools will allow production of transgenic animals, even in nonmodel fish species, to reveal molecular mechanisms essential for stress adaptation. This fundamental knowledge may have relevance to improving the welfare of the organism in aquaculture and for protecting ecosystem health and biodiversity.