Nongenomic cortisol signaling in fish

Glucocorticoids are critical regulators of the cellular processes that allow animals to cope with stressors. In teleosts, cortisol is the primary circulating glucocorticoid and this hormone mediates a suite of physiological responses, most importantly energy substrate mobilization that is essential for acute stress adaptation. Cortisol signaling has been extensively studied and the majority of work has been on the activation of the glucocorticoid receptor (GR), a ligand-bound transcription factor, and the associated downstream transcriptional and protein responses. Despite the role of this hormone in acute stress adaptation, very few studies have examined the rapid effects of this hormone on cellular function. The nongenomic corticosteroid effects, which are rapid (seconds to minutes) and independent of transcription and translation, involve changes to second-messenger pathways and effector proteins, but the primary receptors involved in this pathway activation remain elusive. In teleosts, a few studies suggested the possibility that GR located on the membrane may be initiating a rapid response based on the abrogation of this effect with RU486, a GR antagonist. However, studies have also proposed other signaling mechanisms, including a putative novel membrane receptor and changes to membrane biophysical properties as initiators of rapid signaling in response to cortisol stimulation. Emerging evidence suggests that cortisol activates multiple signaling pathways in cells to bring about rapid effects, but the underlying physiological implications on acute stress adaptation are far from clear.