Induction of corticotropin-releasing hormone gene expression by glucocorticoids: implication for understanding the states of fear and anxiety and allostatic load.
Evidence supports the idea of two distinct corticotropin-releasing hormone (CRH) systems in the brain: one which is constrained by glucocorticoids and the other which is not. It is this latter system that includes two primary sites (central nucleus of the amygdala and the lateral bed nucleus of the stria terminalis) in which the regulation of CRH gene expression can be disassociated from that of the paraventricular nucleus of the hypothalamus. It is this other system that we think is linked to fear and anxiety and to clinical syndromes (excessively shy fearful children, melancholic depression, post-traumatic stress disorder and self-administration of psychotropic drugs). The excess glucocorticoids and CRH, and the state of anticipatory anxiety, contribute to allostatic load, a new term that refers to the wear and tear on the body and brain arising from attempts to adapt to adversity.
Department of Physiology and Biophysics, Georgetown University, Washington, DC, USA. jay@codon.nih.gov
J
J
Schulkin
P W
PW
Gold
B S
BS
McEwen
D000223:Adaptation, Psychological / Q000502:physiology; D000328:Adult; D000818:Animals; D001007:Anxiety / Q000235:genetics / Q000503:physiopathology*; D001143:Arousal / Q000235:genetics / Q000502:physiology*; D001921:Brain / Q000503:physiopathology; D001931:Brain Mapping; D002648:Child; D003345:Corticosterone / Q000097:blood; D003346:Corticotropin-Releasing Hormone / Q000235:genetics*; D005239:Fear / Q000502:physiology*; D015870:Gene Expression / Q000502:physiology*; D005938:Glucocorticoids / Q000502:physiology*; D006801:Humans; D051381:Rats
D005938:Glucocorticoids; D003346:Corticotropin-Releasing Hormone; D003345:Corticosterone