Role of brain, pituitary and spleen corticotropin-releasing factor receptors in the stress response.

Abstract

CRF plays a fundamental role in integrating stress-related responses throughout the neuro-immuno-endocrine axis. Its endocrine effects include actions at the pituitary level to stimulate the synthesis and release of POMC-derived peptides. CRF acts within the CNS to integrate the autonomic, behavioral, endocrine and immune responses to stress. Furthermore, recent evidence suggests that CRF may have direct actions on immunocytes to modulate immune function in the periphery. The actions of CRF in CNS, pituitary, and spleen are mediated by specific, high-affinity membrane receptors with similar kinetic and pharmacological properties. CRF receptors in these various tissues are functionally linked to a guanine nucleotide binding protein mediating stimulation of adenylate cyclase activity. Chemical affinity cross-linking studies demonstrated that the molecular weight of the CRF receptor-binding protein is different in central versus peripheral tissues and that the differences observed in molecular weights are due to the microheterogeneity of the carbohydrate moieties on the receptors in the two types of tissues. In autoradiographic studies, CRF receptors were localized in highest densities in anterior and intermediate lobes of the pituitary, and in brain regions involved in cognitive function, in limbic areas involved in emotion and in brain areas regulating autonomic and other stress-related responses. In spleen, CRF binding sites were localized in the macrophage-rich red pulp and marginal zones surrounding the white pulp regions. Studies examining the effects of CRF administration on local cerebral glucose utilization demonstrated differential changes in glucose utilization in brain regions that have been implicated in mediating the effects of CRF in a variety of homeostatic systems and the organism's ability to respond to stress. Overall, these data provide additional evidence for a physiological role for CRF in the brain-endocrine-immune axis and further support the importance of this neuro-peptide in coordinating the response to stress.