Immunohistochemical visualization of corticotropin-releasing factor type 1 (CRF₁) receptors in monkey brain

Corticotropin-releasing factor receptor type 1, CRF₁, plays a prominent role in the hypothalamic-pituitary-adrenal (HPA) axis and is implicated in the autonomic and behavioral responses to stress. Dysregulation of the CRF system may underlie the pathophysiology of several disorders, including depression and anxiety. The distribution of CRF₁ mRNA and CRF ₁ specific ligand binding has been reported by multiple groups in rodents using in situ hybridization and receptor autoradiography, respectively. More recently, somewhat conflicting rodent anti-CRF₁ immunohistochemical studies were reported. In this study we report the generation of an antihuman CRF₁ antiserum and provide the first immunohistochemical description of CRF₁ distribution in a primate brain, that of the rhesus monkey. The specificity of anti-CRF-R1 antiserum R221 was demonstrated using transfected hCRF₁-expressing HEK 293 cells and rhesus monkey pituitary. CRF₁-immunoreactive neurons were widespread in the rhesus brain. CRF₁ staining was associated with neuronal cell bodies and dendrites and was primarily intracellular, suggesting a high rate of receptor turnover or receptor sequestration. Anti-CRF₁ immunoreactivity was most abundant in pituitary, cerebellum, and in portions of brain stem associated with sensorimotor function. CRF₁ staining was also observed in cerebral cortex, basal forebrain, portions of the basal ganglia, and thalamus. Staining was relatively low in prefrontal cortex and in limbic areas, which may reflect masking of the N-terminal epitope. The distribution of CRF₁ immunoreactivity is suggestive of roles in attentional processing as well as the processing of motor and sensory information.