Novel aspects of glucocorticoid actions (original) (raw)

2014, Journal of Neuroendocrinology

Living organisms are constantly faced with external and internal challenges or stressors threatening the internal environment equilibrium or homeostasis (1). Adaptation to this changing environment requires the coordinated activation of multiple neuroendocrine responses, prominently including activation of the hypothalamic pituitary adrenal (HPA) axis (2). Control of HPA axis activity is complex, involving sensors conveying signals to corticotrophin-releasing hormone (CRH) neurones in the hypothalamic paraventricular nucleus (PVN), either through direct neural connections, or indirectly through pathways relaying on limbic structures such as the amygdala, frontal cortex, bed nucleus of the stria terminalis and hippocampus (2). CRH and vasopressin (AVP), released from parvocellular neurones of the PVN into the pituitary portal circulation, increase the secretion of adrenocorticotrophic hormone (ACTH) from pituitary corticotrophs, which in turn stimulates glucocorticoid (GC) secretion from the adrenal. The HPA axis is highly conserved through evolution, with its components being present in early vertebrates. The secretion of GCs (i.e. cortisol in humans, corticosterone in rats and mice) is episodic, following circadian (daily) and ultradian (hourly) rhythms, and shows marked but transient increases after exposure to stressors. This episodic nature of GC secretion is critical for the transcriptional activity of the steroid .