Characterization and regulation of corticotropin-releasing factor receptors in the central nervous, endocrine and immune systems.

Corticotropin-releasing factor (CRF) plays a major role in coordinating the endocrine, autonomic, behavioural and immune responses to stress through actions in the brain and in the periphery. CRF receptors identified in brain, pituitary and spleen have comparable kinetic and pharmacological characteristics, guanine nucleotide sensitivity and adenylate cyclase-stimulating activity. Differences were observed in the molecular mass of the CRF receptor complex between brain (58,000 Da) and pituitary and spleen (75,000 Da), which appeared to be due to differential glycosylation of the receptor proteins. In autoradiographic studies, CRF receptors were localized in highest densities in anterior and intermediate lobes of the pituitary, olfactory bulb, cerebral cortex, amygdala, cerebellum and the macrophage-rich marginal zones and red pulp regions of the spleen. CRF can modulate the number of CRF receptors in both the brain and pituitary in a reciprocal manner. The demonstration of functional CRF receptors in brain, pituitary and spleen suggests the importance of this neuropeptide in integrating the responses of the CNS, endocrine and immune systems to physiological, psychological and immunological stimuli.