Chapter 8 - The Hypothalamic–Pituitary–Adrenal Axis and Neuroendocrine Responses to Stress

Abstract

External or internal stressful stimuli threatening homeostasis induce coordinated responses, including behavioral, autonomic nervous system and endocrine changes, aimed at restoring the internal equilibrium. Activation of the hypothalamic pituitary adrenal (HPA) axis involves stimulation of a specific group of neurons located in the dorsomedial parvocellular subdivision of the paraventricular nucleus (PVN) of the hypothalamus. CRH exerts its effects in the pituitary corticotrope and other target cells by binding toplasmamembrane receptors coupled to adenylate cyclase via guanyl nucleotide binding protein. The distribution of CRH receptors in the brain is consistent with the pivotal role of CRH as a mediator of the integral stress responses. Diencephalic structures expressing abundant CRHR1 include the dorsomedial hypothalamic nucleus, dorsolateral thalamic nuclei, supramammillary nuclei, anterior paraventricular thalamic nuclei and arcuate nucleus. Acute stress causes rapid activation of parvocellular CRH neurons as shown by the rapid increases in c-fos and CRH primary transcripts, the latter indicating transcriptional activation of the CRH gene.