Role of glucocorticoid in developmental programming: evidence from zebrafish

The vertebrate corticosteroid stress response is highly conserved and a key function is to restore homeostasis by mobilizing and reallocating energy stores. This process is primarily initiated by activation of the hypothalamus-pituitary-adrenal axis, leading to the release of corticosteroids into the circulation. In teleosts, cortisol is the primary corticosteroid that is released into the circulation in response to stress. This steroid activates corticosteroid receptors that are ligand-bound transcription factors, modulating downstream gene expression in target tissues. Recent research in zebrafish (Danio rerio) has identified novel roles for cortisol in early developmental processes, including organogenesis and mesoderm formation. As cortisol biosynthesis commences only around the time of hatch in teleosts, the early developmental events are orchestrated by cortisol that is maternally deposited prior to fertilization. This review will highlight the molecular events leading to the development of the corticosteroid stress axis, and the possible role of cortisol in the developmental programming of stress axis function. Use of zebrafish as a model may lead to significant insights into the conserved role of glucocorticoids during early development with potential implications in biomedical research, including fetal stress syndromes in humans.