Extent and role of urogastrone in the adaptive response of rat intestine to patching of a surgical defect in the ileum

Crypt cell production rate, morphometric changes and uptake of radiolabeled human urogastrone (¹²⁵I rhUG) were evaluated in intestinal tissues of the rat at 2, 4, 8, and 12 days following patching of a surgical defect in the ileum with adjacent cecum. The terminal ileum was incised along its antimesenteric border and the margin of the opened ileum was sutured onto the serosal surface of the cecum. At autopsy, the animals were injected intraperitoneally with 1 μg/g body weight of the metaphase arrest agent, vincristine sulfate, and 50 μCI of ¹²⁵I-rhUG (specific activity 1.7 μCi/μg) to quantify the crypt cell production rate and uptake of radiolabeled urogastrone, respectively. The results indicated that the crypt cell production rate was increased significantly throughout the small intestine of operated animals till the 12th postoperative day as compared to unoperated rats. The colon showed significantly increased crypt cell production rate only on the 4th day after surgery compared to unoperated rats. The stomach showed no changes. The uptake of ¹²⁵I-rhUG increased significantly on the 2nd and 4th postoperative days in the small intestine and on the 2nd postoperative day in the colon as compared to unoperated rats and gradually decreased with increasing time after surgery. These results suggest that patching of an ileal defect resulted in a strong compensatory response in the small intestine. These results also demonstrated a close association between epithelial cell proliferation and uptake of ¹²⁵I-rhUG, particularly in the early part of intestinal adaptation following the surgical stimulus to ileum. However, these data do not identify whether the increased uptake of ¹²⁵I-rhUG is the cause or the effect of proliferation induced by a surgical stimulus. Further analysis also revealed that there was a significant correlation between crypt cell production rate and crypt depth in the small intestine, and crypt depth had a significant correlation with ¹²⁵I-rhUG uptake in the duodenum and jejunum. The crypt cell production rate was inversely correlated with villus height in the ileum adjacent to the site of surgical patching. These results suggest that a villus-to-crypt inhibitory feedback mechanism is an important regulator of crypt cell production at local sites. Furthermore, an additional compensatory mechanism of increased cell production throughout the small intestine exists which is associated with increased urogastrone/epidermal growth factor (URO/EGF) binding. However, this increase in URO/EGF binding is likely a surrogate marker for increased numbers of immature crypt cells; therefore, the regulator of this adaptive response remains to be identified.