Urocortin and corticotropin-releasing factor receptor expression in the human colonic mucosa

Urocortin is a newly identified member of the CRF neuropeptide family. Uroc ortin has been found to bind with high affinity to CRF receptors, The prese nt study investigated urocortin and CRF receptor expression in human coloni c mucosa. Non-pathologic sections of adult colorectal tissues were obtained from patients with colorectal cancer at surgery. Urocorlin expression was examined using immunohistochemistry and messenger (m) RNA in situ hybridiza tion. Isolated lamina propria mononuclear cells (LPMC) and epithelial cells were also analyzed by flow cytometry for the characterization of urocortin -positive cells, and by RT-PCR for detection of urocortin, CRF, and CRF rec eptor mRNA. Urocortin peptide distribution at various stages of human devel opment (n = 35, from 11 weeks of gestation to 6 years of age) was examined by immunohistochemistry using surgical and autopsy specimens. Immunoreactiv e urocortin and urocortin mRNA were predominantly detected in lamina propri a macrophages. Urocortin peptide expression was detected from as early as t hree months of age, but not before birth or in neonates. Urocortin, CRF rec eptor type and type 2 alpha mRNA were detected in LPMC. CRF receptor type 2 beta mRNA, a minor isoform in human tissues, was also detected in LPMC, bu t at lower levels. Urocortin is locally synthesized in lamina propria macro phages and may act on lamina propria inflammatory cells as an autocrine/par acrine regulator of the mucosal immune system. The appearance of urocortin after birth indicates that the exposure to dietary intake and/or luminal ba cteria after birth may contribute to the initiation of urocortin expression in human gastrointestinal tract mucosa. (C) 2000 Elsevier Science Inc. All rights reserved.