Modulation of binding sites for corticotropin-releasing hormone by chronic psychosocial stress

This study was conducted to determine whether long lasting psychosocial stress would affect corticotropin-releasing hormone (CRH) binding sites in the brain, the pituitary, and the adrenal gland. As a model for sustained emotional stress we used chronic psychosocial conflict in male tree shrews. In subordinate tree shrews, repeated confrontation with a dominant conspecific results in constant hyperactivity of the HPA-axis and an elevated neurosympathetic tone. After 24 days of psychosocial conflict, CRH binding sites were quantified by in vitro-autoradiography with 125I-ovine CRH in 23 discrete brain regions, the pituitaries, and the adrenal glands of subordinate and control animals. Chronic stress significantly reduced the number of binding sites (Bmax) in the anterior lobe of the pituitary, the dentate gyrus, the CA1-CA3 areas of the hippocampus, and in both the stratum griseum superficiale and the stratum opticum of the superior colliculus. In cortical area 17, the reduction of Bmax was counterbalanced by an increase in the affinity (Kd) of the radioligand for the binding sites. A significant stress-induced enhancement of Bmax was observed in the frontal cortex, cingulate cortex, claustrocortex, the central and lateral nucleus of the amygdala, and in the choroid plexus. This increase was accompanied by a significant decrease of Kd-values in the frontal and cingulate cortex, the lateral nucleus of the amygdala, and the choroid plexus. These findings represent the first in vivo demonstration of a modulation of extrahypothalamic CRH receptors by a naturally occurring form of stress. The different response patterns of the central CRH binding sites reflect distinct neuroendocrine processes which are presumed to coordinate behavioral, autonomic, endocrine, and immune responses to long-lasting psychosocial conflict.