Corticotropin-releasing hormone and its receptors: an evaluation at the transcription level in vivo

Activation of the hypothalamic-pituitary-adrenal (HPA) axis is the main defining feature of the stress response. The primary mediator of this response is corticotropin-releasing hormone (CRH), a 41-residue peptide acknowledged as the principal hypophysiotropic factor driving stress-induced adrenocorticotropic hormone (ACTH) secretion. Although CRH is widely distributed within the central nervous system (CNS). the paraventricular nucleus (PVN) of the hypothalamus is the principal site of the parvocellular neurosecretory neurons responsible for delivering CRH to the hypophyseal portal system, an event that initiates the activity of the pituitary-adrenal axis. Stress-induced transcriptional activation of CRH takes place quite uniquely in this hypothalamic nucleus, despite the robust constitutive hybridization signal for CRH mRNA across the brain. The fact that CRH itself is capable of mimicking these effects and that de novo but transient expression of its type one receptor occurs in the PVN are data that make this hypothalamic region of great interest to study the mechanisms that lead to such specific transcriptional activity. This review will present evidence of such phenomenon by stressors of different categories as well as the possible neuromediators involved. (C) 2001 Elsevier Science Inc. All rights reserved.