Genomic and nongenomic cortisol signaling in fish

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Stress is part and parcel of life. One of the acute responses to stress is the production of corticosteroids and this is seen in all vertebrates studied. The predominant corticosteroid produced in response to stress in most vertebrates is cortisol. The stimulation by this steroid hormone brings about several molecular, biochemical and physiological changes, and is consistent with the important role this hormone is thought to play in stress adaptation. However, a cause and effect relationship between stressor exposure and the benefits of this highly conserved steroid response is still lacking. This is because we know so little about the mode of action of this steroid in allowing animals to cope with stress. Cortisol action involves two key proteins, the glucocorticoid receptor (GR) and mineralocorticoid receptor (MR), which relay information that results in gene expression changes (genomic signaling). Recent studies suggest yet another mode of action of cortisol that results in rapid effects, but independent of GR and MR activation (nongenomic signaling). However, the mechanisms are far from clear. This proposal intends to describe the role of these cortisol signaling pathways in the development of corticosteroid production, and stress coping mechanisms. Using zebrafish and rainbow trout, a cause and effect relationship in response to cortisol signaling will be established by using gene knockdown and pharmacological methods. Specifically, using genome and phosphoproteome analyses, this study will identify the regulatory gene and protein networks modified by cortisol signaling in a receptor-dependent and receptor-independent fashion. The overall goal is to discover novel pathways involved in cortisol signaling and will establish a mechanistic link between this steroid secretion and stress adaptation.