The roles of the corticotropin-releasing factor system in amphibians

Corticotropin-releasing factor (CRF) is the principle neurohormone responsible for activating the vertebrate stress response. While CRF is known to coordinate the endocrine, behavioral and autonomic responses to stress through actions in the brain and the periphery of mammals, comparatively little information is available in other vertebrates. To better understand the evolution of the integrated stress system, I studied multiple physiological roles of the CRF system in amphibians.; CRF has been implicated in the control of amphibian metamorphosis via its stimulatory effect on the larval thyroid axis, suggesting a potential mechanism for environmental effects on metamorphic acceleration. However, few studies have compared hormonal changes while manipulating environmental factors. I show that both water volume reduction and food deprivation accelerated spadefoot tadpole development and increased whole body TH content. Tadpoles exposed to low water levels exhibit brain-region specific changes in CRF peptide content suggesting activation of CRF neuronal physiology. CRF injections can also accelerate metamorphosis in Ambystoma tigrinum larvae and increase whole body thyroid hormone (TH) content in Xenopus laevis tadpoles.; In addition to its neuroendocrine role, the components of the CRF system are expressed in many peripheral tissues in X. laevis, suggesting multiple physiological roles. One such role is as growth/survival factor in tadpole tail. I show that CRF inhibits regression of tail explants and stimulates proliferation of XLT-15 cells (derived from Xenopus tail myoblasts). Increasing concentrations of CRF-binding protein during metamorphosis may inhibit CRF effects.; I have identified and characterized two novel amphibian CRF-like peptide ligands, urocortin 1 and urocortin 3, from X. laevis. RT-PCR analysis demonstrated that both genes are expressed in brain, pituitary, heart, and kidney. CRF1 and CRF-binding protein (CRF-BP) exhibited a higher affinity for CRF than for UCN1. Similar to rodent and humans, UCN3 appears to be a selective ligand for CRF2 and is not bound by CRF-BP.; My findings support the hypothesis that CRF mediates development responses to environmental stress in both salamander and anuran larvae through its activation of the thyroid axis and that the CRF system and its role in central and peripheral tissues appear to have evolved early in vertebrate evolution.