The principal effectors of the stress response are localized in the paraventricular nucleus (PVN) of the hypothalamus, the anterior lobe of the pituitary gland, and the adrenal gland. This collection of structures is commonly referred to as the hypothalamic-pituitary-adrenal (HPA) axis (Figure 1). In addition to the HPA axis, several other structures play important roles in the regulation of adaptive responses to stress. These include brain stem noradrenergic neurons, sympathetic andrenomedullary circuits, and parasympathetic systems.5-7 Figure 1. Schematic Inhibitors,research,lifescience,medical representation of the hypothalamic-pituitary-adrenal (HPA)

axis. Hypophysiotropic neurons localized in the paraventricular nucleus (PVN) of the hypothalamus synthesize corticotropin-releasing factor (CRF) and vasopressin (AVP). In response to … The HPA axis Hypophysiotropic neurons localized in the medial parvocellular subdivision of the PVN synthesize Inhibitors,research,lifescience,medical and secrete corticotropin-releasing factor (CRF), the principle regulator of the HPA axis.8,9 In response to stress,

CRF is released into hypophysial portal vessels that access the anterior pituitary gland. Binding of CRF to its receptor on pituitary corticotropes induces Inhibitors,research,lifescience,medical the release of adrenocorticotropic hormone (ACTH) into the systemic circulation. The principal target for circulating ACTH is the adrenal cortex, where it stimulates glucocorticoid synthesis and secretion from the zona

fasciculata. Glucocorticoids are the downstream effectors of the HPA axis and regulate physiological changes through ubiquitously distributed intracellular receptors.10,11 The biological effects of glucocorticoids Inhibitors,research,lifescience,medical are usually adaptive; Blebbistatin however, inadequate or excessive activation of the HPA axis may contribute to the development of pathologies.10,12 The CRF family of peptides Corticotropin-releasing factor is a 41 amino acid peptide that was originally isolated from ovine hypothalamic Inhibitors,research,lifescience,medical tissue in 1981. 8 Since this initial identification, CRF has been shown to be the primary regulator of ACTH release from anterior pituitary corticotropes9 and has also been implicated in the regulation of the autonomic nervous system, learning and memory, feeding, and reproductionrelated behaviors.13-19 CRF is widely expressed through-out the central nervous Nature Reviews Genetics system (CNS) and in a number of peripheral tissues. In the brain, CRF is concentrated in the medial parvocellular subdivision of the PVN and is also localized in the olfactory bulb, bed nucleus of the stria terminalis (BNST), medial preoptic area, lateral hypothalamus, central nucleus of the amygdala, Barington’s nucleus, dorsal motor complex, and inferior olive.20 In the periphery, CRF has been detected in the adrenal gland, testis, placenta, gastrointestinal tract, thymus, and skin.21-23 Three additional members of the CRF peptide family have recently been identified.