The teleost corticotropin-releasing factor system: distribution, regulation, and developmental role
This thesis is an investigation of the distribution, regulation, and functions of the corticotropin-releasing factor (CRF) system in teleosts, with a particular emphasis on its role in stress adaptation beyond the hypothalamus-pituitary-interrenal (HPI) axis. The teleost CRF system (neuropeptides, CRF and urotensin I (UI); receptors; binding protein, CRF-BP) is best known for its role in regulating the HPI axis through stimulation of adrenocorticotropin release; however, it also functions in behavioural and autonomic responses to stress, and may play a role in development. The extent to which CRF-BP is involved in these functions is poorly understood; therefore I characterized the expression of CRF-BP in the adult rainbow trout using a combination of quantitative and histochemical techniques (Chapter 2). I found that CRF-BP is extensively expressed in the brain, and demonstrated regional- and stressor-specific changes in its gene expression in socially subordinate and hypoxia-exposed fish. By mapping for the first time in fish the relative distributions of CRF, UI, and CRF-BP mRNAs in adult zebrafish brains, I was able to corroborate expression patterns with known CRF system functions, propose shared and unique functions for CRF and UI, and describe a close association between the expression patterns of CRF-BP and CRF (Chapter 3). Stress experienced at critical points in development can pose lifelong phenotypic changes. As a preliminary step in understanding the potential involvement of the CRF system in mediating the effects of early life experience on adult fitness, I characterized the ontogeny of the CRF system and assessed the timing of HPI axis responsiveness to stress in developing zebrafish (Chapter 4). I showed that the expression of the CRF system long precedes the onset of HPI axis functionality; therefore, I hypothesized that CRF plays an HPI axis-independent role in zebrafish development. I over-expressed CRF by mRNA microinjection and showed reduced caspase-3/7 activity in heat shock exposed embryos, suggesting that CRF may playa role in suppressing stress-induced apoptosis during embryogenesis (Chapter 5). 'Overall, this thesis provides novel data that supports a diverse role for the CRF system in teleosts, and describes for the first time a role for CRF in fish development'.