RESUMEN
The enteroendocrine cell system of the mammalian gastrointestinal tract is comprised of at least 16 different subpopulations. Each subpopulation shows a characteristic distribution along both the crypt-villus and cephalo-caudal axes. In both the small intestine and colon of adult mice, multilabel immunohistochemistry has demonstrated that two or more neuroendocrine products can be coexpressed in various combinations in single cells along the crypt-villus axis, suggesting that enteroendocrine phenotypes may be actively regulated. Using bromodeoxyuridine (BrdU) incorporation and multilabel immunohistochemistry, we have previously demonstrated an enteroendocrine cell differentiation pathway consisting of two subpopulations of cells in the mouse proximal small intestine--one involving the sequential expression of substance P, serotonin, and secretin in cells migrating out of the crypts into the villi, and a second involving the expression of substance P and serotonin in cells which remain in the crypts. In this report, we use double label immunohistochemistry and BrdU incorporation to define the temporal and spatial interrelationships between gastrin, cholecystokinin (CCK), glucagon-like peptide-1 (GLP-1), and gastric inhibitory peptide (GIP) immunoreactive cells in the mouse proximal small intestine. The expression of these products was compared with that of substance P, serotonin, and secretin. Minimal overlap of expression was found in cells immunoreactive for substance P or serotonin with gastrin, CCK, GLP-1, or GIP; however, secretin was found colocalized in villus-associated gastrin, CCK, and GLP-1 containing cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Glándulas Endocrinas/química , Hormonas Gastrointestinales/análisis , Mucosa Intestinal/química , Intestino Delgado/química , Animales , Bromodesoxiuridina , Diferenciación Celular , Glándulas Endocrinas/citología , Glándulas Endocrinas/metabolismo , Femenino , Hormonas Gastrointestinales/biosíntesis , Inmunohistoquímica , Mucosa Intestinal/citología , Mucosa Intestinal/metabolismo , Intestino Delgado/citología , Intestino Delgado/metabolismo , RatonesRESUMEN
BACKGROUND/AIMS: Enteroendocrine cell subpopulations are uniquely distributed along the crypt-villus and cephalocaudal axes of the small intestine. These regional differences in enteroendocrine cell expression, which are maintained in spite of rapid turnover of the epithelium, serve as descriptive markers of physiological differences along the length of the bowel. This study aimed to determine the influence of luminal contents on the maintenance of regional differentiation patterns of enteroendocrine and enterocytic phenotypes. METHODS: Sections of jejunum and ileum were surgically transposed in rats, leaving the innervation and blood supply to the transposed segments intact. The animals were killed 1, 4, and 8 weeks after surgery. Enteroendocrine cell subpopulations and enterocytic cell markers were studied immunohistochemically. RESULTS: No change in regional expression patterns was seen in response to the altered luminal environment by any of the enterocytic markers and four of the five enteroendocrine cell subpopulation markers. Eight weeks after surgery, the number of gastrin-expressing enteroendocrine cells increased in ileal segments transplanted proximally. CONCLUSIONS: Although luminal signals can affect intestinal stem cells to alter their proliferation rates, the luminal environment has only limited effects on the regional-specific expression of enteroendocrine or enterocytic products.
Asunto(s)
Adaptación Fisiológica , Glándulas Endocrinas/fisiología , Íleon/trasplante , Intestinos/fisiología , Yeyuno/trasplante , Proteínas de Neoplasias , Proteínas del Tejido Nervioso , Trasplante Heterotópico , Animales , Biomarcadores , Proteínas Portadoras/metabolismo , Glándulas Endocrinas/citología , Proteína de Unión a los Ácidos Grasos 7 , Proteínas de Unión a Ácidos Grasos , Gastrinas/metabolismo , Péptidos Similares al Glucagón , Inmunohistoquímica , Mucosa Intestinal/metabolismo , Intestinos/citología , Hígado/metabolismo , Masculino , Péptidos/metabolismo , Ratas , Ratas Sprague-DawleyRESUMEN
Precise spatial interrelationships exist between substance P, serotonin, and secretin containing enteroendocrine cells in the gastrointestinal tract of mice. In the proximal small intestine these products are coexpressed in various combinations in single enteroendocrine cells along the crypt to villus axis in a pattern that suggests the sequential expression of substance P, serotonin, and secretin. In this report we use bromodeoxyuridine (BrdU) and multilabeling immunohistochemistry to define the temporal and spatial interrelationships between substance P, serotonin, and secretin immunoreactive cells in the mouse proximal small intestine. Our findings demonstrate the sequential expression of substance P, serotonin, and secretin in a population of upwardly migrating enteroendocrine cells and, furthermore, identify a population of crypt associated cells coexpressing substance P and serotonin that fails to traverse this pathway. The lack of secretin immunoreactive cells in the crypts suggests that local factors present in the crypts and/or on villi regulate secretin expression. The combined use of BrdU and multilabeling immunohistochemistry provides a method for defining enteroendocrine cell differentiation pathways throughout the gastrointestinal tract.