1. The objective of this study was to see whether another proliferative stimulus could modify the marked proliferative effect of human epidermal growth factor (urogastrone-epidermal growth factor, URO-EGF) on the gastrointestinal epithelium.
2. The response of the gastrointestinal tract to URO-EGF was investigated in rats maintained on total parenteral nutrition (TPN) with or without 75% small bowel resection.
3. Continuous infusion of 60 μg of recombinant β-urogastrone/day per rat increased proliferation in the stomach by over four times (P < 0.01), doubled proliferation in the small intestine (P < 0.001) and increased it by four and a half times in the colon (P < 0.001) in the control group. No significant effect of urogastrone was observed in the stomach of the resected groups, but proliferation was also increased in the small intestine by one and a half times (P < 0.001) and by nearly four times in the colon (P < 0.001).
4. Two-way analysis of variance showed that resection had a significant effect (P < 0.01) on proliferation below the anastamosis and in the ileum. However, the response of the ileum was only half that observed in orally fed rats, which confirms the importance of ‘luminal nutrition’ in the response to resection.
5. Intestinal resection in the TPN rat was associated with a small rise in plasma enteroglucagon levels, suggesting that this hormone may be implicated in the adaptive response of the small intestine to resection. However, the proliferative effects of URO-EGF were not associated with increased plasma enteroglucagon and thus the two agents probably exert their proliferative effects via separate mechanisms.
6. There was no evidence for a significant positive interaction between the effects of URO-EGF and resection. Thus loss of intestinal mass had no influence on the susceptibility of the intestine to the effects of URO-EGF. Although URO-EGF significantly increased intestinal epithelial cell proliferation, it could not entirely compensate for the lack of luminal contents.