The Central Distribution of a Corticotropin-Releasing Factor (CRF)-Binding Protein Predicts Multiple Sites and Modes of Interaction with CRF

• Published in: Proceedings of the National Academy of Sciences - PNAS 1992-05, Vol.89 (9), p.4192-4196
• Main Authors: Potter, Ellen, Behan, Dominic P., Linton, Elizabeth A., Lowry, Philip J., Sawchenko, Paul E., Vale, Wylie W.
• Format: Article
• Language: English
• Subjects: Adrenocorticotropic Hormone - metabolism; Amygdala; Analytical, structural and metabolic biochemistry; Animals; Antiserum; Binding and carrier proteins; Biological and medical sciences; Brain; Brain - physiology; Carrier proteins; Carrier Proteins - genetics; Carrier Proteins - metabolism; Cell nucleus; Cellular biology; Corticotropin-Releasing Hormone - metabolism; Fundamental and applied biological sciences. Psychology; Gene Expression; Male; Medical research; Messenger RNA; Neurons; Neurosecretory cells; Nucleic Acid Hybridization; Pituitary Gland, Anterior - metabolism; Proteins; Pyramidal cells; Rats; Rats, Inbred Strains; Ribonucleic acid; RNA; RNA, Messenger - genetics
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.89.9.4192

In recent studies to clone and characterize genes coding for the corticotropin-releasing factor-binding protein (CRF-BP), analysis of the tissue distribution of the CRF-BP gene indicated a high level of expression in the rat brain. We have now characterized by immunohistochemical and hybridization histochemical means the cellular localization of CRF-BP protein and mRNA expression, respectively. Results from both approaches converged to indicate that CRF-BP is expressed predominantly in the cerebral cortex, including all major archi-, paleo-, and neocortical fields. Other prominent sites of mRNA and protein expression include subcortical limbic system structures (amygdala, bed nucleus of the stria terminalis), sensory relays associated with the auditory, olfactory, vestibular, and trigeminal systems, several raphe nuclei, and a number of cell groups in the brainstem reticular core. Expression in the hypothalamus appears largely limited to the ventral premammillary and dorsomedial nuclei; only isolated CRF-BP-stained cells are apparent in neurosecretory cell groups. Dual immunostaining for CRF and CRF-BP revealed a partial colocalization in some of these regions. In addition, prominent CRF-BP-stained terminal fields have been identified in association with CRF-expressing cell groups in circumscribed hypothalamic and limbic structures. In the anterior pituitary, CRF-BP mRNA and immunoreactivity were colocalized with corticotropin-immunoreactivity in a majority of corticotropes. Thus, CRF-BP could serve to modify the actions of CRF by intra- and intercellular mechanisms, in CRF-related pathways in the central nervous system and pituitary.