Chronic exposure to subtoxic levels of peroxidized lipids suppresses mucosal cell turnover in rat small intestine and reversal by glutathione

Oxidative challenge can compromise intestinal growth and death responses. This study examines the effect of chronic consumption of subtoxic levels of peroxidized lipids on intestinal redox balance and turnover and the effect of glutathione (GSH) supplementation. Male Sprague-Dawley rats were fed standard rat chow or 4% peroxidized menhaden oil chow (2–8 weeks). Intestinal GSH and glutathione disulfide (GSSG), GSH synthetic and redox enzymes as well as proliferative (ornithine decarboxylase, ODC) and apoptotic activities were evaluated. Chronic peroxide intake did not affect overall animal growth, but decreased intestinal GSH/GSSG ratio that directly correlated with decreased GSH and increased GSSG, and suppressed peak circadian ODC activities and postprandial mucosal apoptosis. Supplementation with GSH restored the mucosal GSH/GSSG ratio and abrogated the peroxide-induced suppression of intestinal cell turnover. Collectively, the results show that chronic lipid peroxide consumption induces intestinal GSH redox imbalance that interferes with regulation of enterocyte death and proliferation in vivo. These disruptive effects of lipid peroxides were reversed by GSH supplementation in accordance with the normalization of tissue GSH/GSSG redox balance.     

Dietary lipids alter the effect of steroids on the uptake of lipids following intestinal resection in rats

Steroids alter the transport function of the intestine. This study was undertaken to assess the effect of glucocorticosteroids on lipid uptake in rats fed either a saturated (SFA) or a polyunsaturated fatty acid (PUFA) diet. Sprague-Dawley rats underwent transection or 50% resection of the small intestine. The steroids had no effect on the uptake of lipids. However, resection decreased the jejunal uptake of palmitic acid in animals fed SFA and increased the jejunal uptake of palmitic and linoleic acids in those fed PUFA. In animals undergoing intestinal resection, fed SFA, and given control vehicle, there was a reduction in jejunal proglucagon mRNA expression as compared to those fed chow or PUFA. Ornithine decarboxylase (ODC) mRNA expression in the jejunum of resected animals was reduced. In summary, dietary lipids modify the uptake of lipids in resected animals and ODC and proglucagon may be involved in this adaptive response.     

Lipid accumulation in jejunal and colonic mucosa following chronic cholestyramine (Questran) feeding

The hypolipidemic agent, cholestyramine (Questran), when fed to rats inhibits intestinal absorption of cholesterol and triglycerides and causes significant epithelial cell damage in both small and large intestine. In this study, we report significant accumulation of lipids in the mucosal layer of both jejunum and colon in rats administered 2% cholestyramine for a four-week period, when compared to a control group maintained on regular chow. The total lipid increment with cholestyramine was 4.7-fold in the jejunum and 3.7-fold in the colon. The triglyceride fraction increased substantially in the small but not the large intestine. Relative phospholipid levels decreased in the treated jejunum but not in the colon. The biochemical data were reflected in morphological evidence of lipid-laden enterocytes obtained by light and transmission electron microscopy. Since cholestyramine has been shown to sequester 99.8% of micellar phospholipidin vitro, it is concluded that the presence of cholestyramine in the intestinal lumen may interefere with phospholipid availability for chylomicron synthesis and serosal lipid exit from the epithelium. This unusual deposition of lipid within the mucosal layer may also be correlated with the known cocarcinogenic effect of this resin in experimentally induced intestinal cancer.Supported by USDA grants 82CRCR 1071 and 82 CRCR 1001.     

Effect of difluoromethyl ornithine (DFMO) on small intestine of adult and weanling rats

Oral feeding ofdl-difluoromethyl ornithine (DFMO) (2% in waterad libitum) for 14 days has no detectable effect on the small intestine of adult rats.Similar feeding of DFMO to weanling rat pups caused diarrhea in three to four days accompanied by a decrease in food consumption and body weight compared to age-matched controls. Significant decreases in small intestinal mucosal weight, total protein, DNA, enterokinase, leucine amino peptidase, sucrase, and maltase contents were observed in the DFMO-treated group four days after treatment. Extending the treatment to seven days led to a more severe reduction in these parameters. Villous atrophy of the mucosa was demonstrable by light microscopy and morphometric measurements. The mucosa of the DFMO-treated rat pups showed a reduction in total thickness and villous height but no change in crypt depth. A significant reduction in villus-crypt ratio was also seen.Changes in small intestinal mucosal parameters were not due to a decrease in food intake since pair-fed, agematched rat pups showed no biochemical changes compared to control pups. DFMO-treated weanling rats showed less than 5% of ornithine decarboxylase (ODC) activity when compared to age-matched control animals. The effects observed on the small intestinal mucosa are presumably due to inhibition of ornithine decarboxylase activities by DFMO which prevents the proliferation, regeneration, and maturation of epithelial cells. The relative insensitivity of the adult rat small intestine to DFMO treatment suggests a lesser dependence of its intestinal mucosa to ODC activities.     

Oral feeding of isolated lectins from red kidney bean stimulates rat small intestinal mucosal DNA synthesis and crypt cell division

A lectin preparation containing enterokinase inhibitor purified or partially purified from red kidney bean (RKB) when fed to weanling rats was shown to cause small intestinal hyperplasia. To see if this hyperplastic effect on the rat small intestine was due to the mitogenic properties of the isolated lectin, male weanling rats were fed a chow containing 0.1% of the isolated lectin for six days. Age-matched control rats were fed regular chow. Both control and lectin-fed rats were sacrificed at one, two, three, four, and six days after the start of lectin feeding. The proximal small intestinal mucosa of rats fed lectin showed gradual increases in protein and DNA contents throughout the experimental period. Morphological studies showed marked increases in crypt depth from days I through 6 in these rats with essentially no change in mucosal thickness or villous height. DNA synthetic activity peaked at day 2, but was higher than control throughout the experimental period. Labeling index was 0.36±0.03 in duodenum of controls as compared to 0.45±0.02 in duodenum of weanling rats fed lectin for two days. These results demonstrate that RKB lectin stimulates overall DNA synthetic activity and increases crypt cell proliferation on the small intestine of weanling rats. The observed mucosal hyperplasia is probably due to increases in crypt cell population as shown by the increase in crypt depth.This study was supported by a grant from the U.S. Agency for International Development.     

Influence of gastrin,gastrin receptor blockers,epidermal growth factor,and difluoromethylornithine on the growth and the activity of ornithine decarboxylase of colonic carcinoma cells

Summary Polyamines are essential factors of cell growth and differentiation. Modulation of the cellular polyamine content by 2-difluoromethylornithine (DFMO) inhibiting ornithine decarboxylase (ODC), or by hormones inducing ODC, influences cell growth. Gastrin acts trophically on some colonic carcinomas and their growth is inhibited by gastrin receptor blockers. The mechanism of the trophic action of gastrin on colonic carcinomas is not known. In this study the effect of gastrin, gastrin receptor blockers, epidermal growth factor (EGF) and DFMO on growth and ODC activity of four human colon carcinoma cell lines (SW 403, SW 1116, LS 174 T and Lovo) was investigated. Growth and ODC activity of all cell lines were inhibited by DFMO. Growth of the SW 403 cell line was increased by gastrin and inhibited by the gastrin receptor blocker benzotrypte. The other cell lines did not respond to gastrin and the gastrin receptor blocker. In SW 403 cells ODC activity was increased by gastrin, and was also elevated after treatment with the gastrin receptor blocker. These in vitro results were confirmed by studies on tumours that developed from SW 403 cells in nude mice. Combination of benzotrypte and DFMO did not enhance the antiproliferative effect. EGF increased growth of SW 403 cells, but no induction of ODC activity was measured. LS 174 T cells were not stimulated by EGF. Medium replacement was the strongest stimulus of ODC activity in SW 403 cells already inducing ODC after 3 h. During cell culture ODC activity was high after seeding and decreased continuously with increasing cell density. These data suggest that gastrin induces ODC in gastrin-sensitive colonic carcinoma cells. DFMO appears to be a valuable antiproliferative agent in colonic carcinoma cells.Abbreviations ODC Ornithine decarboxylase - DFMO 2-difluoromethylornithine - EGF epidermal growth factor Supported by Deutsche Forschungsgemeinschaft (DFG)     

The trophic effect of epidermal growth factor on morphological changes and polyamine metabolism in the small intestine of rats

This study was undertaken to evaluate the effect of epidermal growth factor (EGF) on the morphological changes and polyamine metabolism in the atrophic small intestinal mucosa of rats caused by feeding elemental diet (ED; Elental^?, Ajinomoto, Tokyo) for several weeks. Four-week-old Wistar male rats were given ad libitum ED (1 kcal/ml) for 4 weeks. The body weight increased to the same extent as the control group fed a pellet diet. However, the small intestine became atrophic: the mucosal wet weight of the jejunum decreased to 70%, while that of the ileum decreased to 60%. EGF (10 Μg/kg) was subcutaneously injected into these rats every 8 hours. Ornithine decarboxylase (ODC) activities of the jejunal and ileal mucosa rose within 12 hours of the initial EGF administration. Mucosal DNA specific activities tended to increase. Next, EGF (30 Μg/kg/day) was intraperitoneally administered with a Mini-osmotic pump for one week. The wet weight, protein and DNA contents of the ileal mucosa increased significantly compared with those of the saline administered controls, while the crypt cell production rate (CCPR) also increased. Histologically, increases in both villus height and crypt depth were confirmed. These findings indicate that EGF causes mucosal proliferation through polyamine metabolism even in the atrophie small intestine of mature rats after ED administration for 4 weeks.     

Uptake of lipids into rabbit jejunum and colon following Ileal resection

This study was undertaken to determine the effect of variations in the dietary content of carbohydrate (sucrose) and intestinal resection on the passive jejunal and colonic uptake of short-, medium-, and long-chain length fatty acids, cholesterol, and decanol. A previously validated in vitro technique was used, and studies were performed in sham-operated control animals and in rabbits submitted to the surgical removal of the distal half of the small intestine. After six weeks feeding of a high- or low-carbohydrate diet, the uptake of lipids was altered, but the direction and extent of changes was different among jejunum, ileum, and colon in control animals, and between the jejunum or colon of control vs resected animals. The intestinal membrane is likely heterogeneous with respect to passive permeability pathways since dietary manipulation of sucrose had a different effect on the uptake of each lipid probe. The finding of lower jejunal and colonic cholesterol uptake in animals fed a high- as compared with a low-carbohydrate diet reflects the importance of dietary effects on intestinal permeation. Studies must now be performed to establish the mechanisms responsible for these diet-related changes in intestinal permeability.     

Proglucagon-Derived Peptides in Intestinal Epithelial Proliferation

Proglucagon-derived peptides have been implicated in the control of intestinal mucosal cell division. To investigate the actions of these peptides on intestinal cell proliferation, different doses of enteroglucagon, oxyntomodulin, glucagon-like peptide-1 (GLP-1) and glucagon-like peptide-2 (GLP-2) were tested in male Wistar rats maintained on total parenteral nutrition. Crypt cell proliferation was assessed by the analysis of arrested metaphases in microdissected crypts. Enteroglucagon and oxyntomodulin had no effect on intestinal weight or cell proliferation. GLP-1 had a slight effect on stomach and small intestinal weights and on epithelial cell proliferation in the small and large intestines. GLP-2 infusion dose-dependently increased the weights of the stomach, small intestine, colon, and cecum and increased crypt cell proliferation in the small and large intestines of parenterally fed rats. In orally fed animals, GLP-2 increased intestinal weight but had little effect on proliferation. Therefore, of the proglucagon-derived peptides, GLP-2 appears to be a major mediator of intestinal epithelial proliferation.     

Increased Colonic Ornithine Decarboxylase Activity in Inflammatory Bowel Disease in Children

The risk of colorectal carcinoma is increased inpediatric-onset inflammatory bowel disease (IBD). Thereis little information available regarding the colonicmucosal proliferative state in children with IBD. The aim of this study was to assesscolonic ornithine decarboxylase (ODC) activity, a markerof cell proliferation, in pediatric IBD patients. ODCactivity was assessed in colonic mucosa from 23 children (7 with ulcerative colitis, 9 with Crohn'sdisease, and 7 controls) undergoing colonoscopicexamination. ODC activities were then compared withdegree of inflammation of biopsied samples. ODCactivities in patients with and without corticosteroidtreatment were also analyzed. The mucosal ODC activitiesof sigmoid colon and rectum were significantly higher(2.5- to 4-fold) in both ulcerative colitis and Crohn's disease. The higher ODC activity wasassociated with increased mucosal inflammation.Moreover, treatment with corticosteroids decreased theODC activity. In conclusion, using ODC activities as a marker of cell proliferation, our resultssuggest that there is a higher colonic mucosalproliferative state in children with IBD. The increasedODC activities were associated with increased colonicmucosal inflammation. Colonic mucosal ODC activity mayprovide an additional parameter to access thetherapeutic efficacy of corticosteroid treatment inpediatric IBD patients.     

Dietary Lipids Alter the Effect of Steroids on the Transport of Fructose Following Intestinal Resection in Rats

BACKGROUND: Glucocorticosteroids alter intestinal morphology and transport. We tested the hypothesis that the desired intestinal adaptive response following intestinal resection may be enhanced further by the locally active steroid budesonide, and by feeding a saturated as compared with a polyunsaturated fatty acid diet. METHODS: An in-vitro uptake method was used to assess intestinal fructose uptake by rats of semisynthetic diets enriched in saturated or polyunsaturated fatty acids, and injected with budesonide or control solution. RESULTS: Budesonide increased ileal fructose uptake in chow and PUFA-fed animals, but reduced jejunal fructose uptake in rats fed SFA. GLUT5 and GLUT2 protein and mRNA did not correlate with changes in fructose uptake. Steroids reduced jejunal proglucagon expression in animals fed chow. Animals fed SFA and given budesonide had a reduction in jejunal ODC mRNA compared with those fed PUFA or chow. CONCLUSIONS: (1) budesonide increases ileal fructose uptake following intestinal resection, and this beneficial effect is prevented by feeding SFA rather than PUFA; (2) fructose uptake does not correlate with GLUT5 and GLUT2 protein and mRNA; (3) ODC and proglucagon may be involved in this adaptive response.     

Suppression of apoptosis is responsible for increased thickness of intestinal mucosa in streptozotocin-induced diabetic rats

Intestinal mucosal growth is a common, but uncharacterized, observation associated with diabetes mellitus. Epithelial homeostasis is balanced by regulation of cell proliferation and cell death. To determine the contribution of apoptosis to the overall maintenance of intestinal growth, we examined intestinal apoptosis in the well-characterized streptozotocin (STZ)-induced diabetes rat model. Rats were injected with STZ (75 mg/kg body weight), thereafter they were allowed free feeding or restricted feeding for 3 weeks. Food intake and intestinal mucosal height were evaluated. In a second experiment, additional groups of animals were injected with STZ and were fed ad libitum for 1 or 3 weeks. Ornithine decarboxylase (ODC) activity, ratio of fragmented DNA to total DNA, electrophoresis of fragmented DNA, and Western blot analysis of caspase-3 were examined. Food intake gradually increased in free-feeding rats after induction of diabetes. Intestinal mucosal height in free-feeding diabetic rats was approximately 25% longer than controls, but this increase in mucosal height was not observed in restricted-fed diabetic rats (25 g/d). ODC activity in intestinal mucosa in diabetic rats did not differ from that of control rats. Percent fragmented DNA of diabetic rats 1 week after STZ injection was significantly lower than that of control rats, and this decrease returned to the control level 3 weeks after STZ treatment. Active form of caspase-3 was attenuated 1 week after drug treatment. Attenuated effect of diabetic rats on intestinal apoptosis did not affect increased apoptosis after ischemia-reperfusion. Suppression of apoptosis in the early days of STZ-induced diabetes was responsible for the increased mucosal height in the small intestine in STZ-induced diabetic animals.     

Epidermal growth factor receptors during postnatal development of the mouse colon

The present study was undertaken to establish the postnatal profile of specific epidermal growth factor (EGF) binding in the maturing mouse colon, with particular emphasis on possible regional differences between both proximal and distal colonic binding patterns vs. those of the small intestine. Binding studies using [125I]EGF were performed on isolated epithelial cells obtained from 2-, 5-, 9-, 16-, and 22-day-old mice as well as adults. At 2 days, cells isolated from the entire colon bound 4 times more [125I]EGF than did corresponding intestinal cells, whereas between the ages of 5 days to adult, colonic cells bound between 1.7-2.5 times more labeled EGF than their intestinal counterparts. The immature colon already exhibited maximal binding after birth as opposed to the small intestine where binding only reached maximal values by the third week of life. Comparison between the proximal and distal colon in 9-, 16-, and 22-day-old mice revealed a further 2-fold increase in EGF binding in the distal colon compared to that in the proximal colon. Scatchard plots of [125I]EGF displacement by native EGF in both proximal and distal colonic segments also revealed the presence of two classes of binding sites, with high affinity constants (K1) significantly greater in the distal colon. These results demonstrate for the first time not only the continued presence of EGF receptors in mouse colonic epithelium, but also significant regional differences in EGF-binding capacity within the digestive tract throughout the postnatal period.     

The effects of glutamine on intestinal epithelial cell proliferation in parenterally fed rats

BACKGROUND: Several papers have indicated that glutamine is a preferred fuel for the enterocyte and that it can increase intestinal epithelial cell proliferation. AIMS: To investigate the effects of glutamine on intestinal epithelial cell proliferation in the parenterally fed rat. METHODS: Five groups of six rats were fed parenterally; a group of orally fed rats was also studied. Crypt cell proliferation was studied after six days using native mitoses in microdissected crypts and bromodeoxyuridine labelling. RESULTS: No effect of treatment was seen on intestinal weight; however, the weights of the small intestine, caecum, and colon were all significantly heavier in the orally fed group than in the total parenteral nutrition groups (p<0.001). There was no effect of any of the glutamine treatments on mitotic activity in the small intestine. In the colon there was a small increase in native mitoses with glutamine (p=0.03). There was also an indication of increased proliferative activity in the first fifth of the small intestine and colon with glutamine. Little effect of glutamine on bromodeoxyuridine labelling in either site was observed, but there was a small but significant reduction in growth fraction of the colon of the glutamine treated group. The labelling distribution curve from sections and the mitotic distribution curve obtained from crypt squashes showed a good correlation. CONCLUSION: Glutamine has a small, but significant effect on mitotic activity but only in the colon. Modest effects on the distribution of labelled cells were also seen.     

Aging and intestinal polyamine metabolism in the rat

Hyperproliferation and delayed expression of enzyme activity occur in small intestinal enterocytes of aging rats, and starvation and refeeding result in impaired control of these processes. Since altered polyamine metabolism may accompany changes in enterocyte proliferation, we studied the effects of nutrient manipulation upon cell numbers, ornithine decarboxylase (ODC) activity and polyamine content in jejunum and ileum of 4- to 5- and 26- to 27-month Fischer rats. In both groups, cell numbers fell during starvation and and increased during refeeding. Crypt cell hyperplasia was found in aging animals. Jejunal putrescine, spermine and spermidine content were greater in older rats, fell during starvation, and rose during refeeding. Ileal ODC activity was 66% greater in the aging rats, but jejunal ODC activity was modestly increased in young animals. Intestinal polyamine content correlates with proliferative changes and polyamine metabolism responds appropriately to nutrient manipulation during aging. Dissociation of ODC activity and polyamine content in aging jejunum probably occurred because enterocyte differentiation was delayed. Investigation of intestinal polyamine metabolism may be useful in elucidating deranged proliferative activities found in the intestine of aging rodents.     

Failure of ornithine decarboxylase inhibition to alter small intestinal epithelial repair after transient segmental ischaemia.

To evaluate the roles of ornithine decarboxylase (ODC) and polyamines in the regulation of epithelial repair, rabbit mid-small intestine after transient ischaemic villus injury in the presence and absence of DL-difluoromethylornithine (DFMO), an irreversible inhibitor of ODC was studied. Rabbits received 2% (w/v) DFMO in drinking water for two days before undergoing a sham laparotomy, or a 90 minute mesenteric vascular occlusion of 20 cm of mid-intestine. DFMO fed and control rabbits were studied four, 24, 72, or 120 hours after this ischaemic intestinal injury. In controls, ischaemic injury caused shortened villi at four hours (p less than 0.01), diminished mucosal sucrase and alkaline phosphatase activities at 24 hours (p less than 0.05), but raised ODC (p less than 0.001) and thymidine kinase (p less than 0.01) activities at four hours with recovery by 72 hours. DFMO treatment significantly reduced ODC activity at all stages of the experiment and significantly inhibited the rise in activity observed after injury (p less than 0.01). Mucosal concentrations of the polyamines, spermidine and spermine, were similar in the sham operated groups; four hours and 24 hours after ischaemia, they increased in the DFMO animals (p less than 0.01) but fell (p less than 0.05) in those that did not receive DFMO. After ischaemic injury, DFMO treatment inhibited ODC but failed to influence recovery of villus structure or enzyme activities in the small intestine. We conclude that ODC and the polyamines, spermidine and spermine, are not key regulators of small intestinal repair after transient ischaemia.     

Medium-chain triglycerides enhance mucous secretion and cell proliferation in the rat

Background  The specific purpose of this study was to investigate the effects of medium-chain triglycerides (MCTs) on intestinal cell proliferation and mucous secretion of the small intestine in the rat. Methods  Rats were fed chow diet and given MCTs or the same weight of corn oil (5 g/kg per day) by gavage daily for 2 weeks, and then tissue samples of the small intestines were harvested. Leptin concentration in the small intestine was measured. Cell proliferation and apoptosis in the small intestine was determined by immunohistochemistry. Diamine oxidase (DAO) activity was measured by colorimetric assay. Results  In rats fed only chow diet (normal rats), the number of goblet cells per villi was 14.2 ± 0.75 in the jejunum and 15.2 ± 1.12 in the ileum. The number of goblet cells increased significantly in rats given MCTs compared with rats given corn oil or normal rats. Ki-67-positive cells were detected on the entire villi and the crypts in the small intestine. Furthermore, the proliferative index and the apoptotic index were also significantly greater in rats given MCTs than rats given corn oil or normal rats. Moreover, DAO activity and leptin concentration in the small intestine were significantly greater in rats given MCTs than rats given corn oil or normal rats. Conclusions  MCTs enhance cell proliferation of the intestinal epithelium and mucous secretion from goblet cells in the small intestine. These effects may protect the gut in patients suffering from inflammatory bowel disease or enterogenous infection.     

Evaluation of intestinal mucosal function by measuring expired (14)CO(2) after oral administration of (14)C-putrescine

BACKGROUND: Diamine oxidase (DAO) is the enzyme that degrades putrescine, the key main product of polyamine metabolism, and reflects enterocytic maturity of absorption because diamine oxidase activity is highest in the small intestine. We have already shown that expired (14)CO(2) after oral administration of (14)C-putrescine correlated with intestinal DAO activity. However, the influence of food composition and the mucosal adaptation after intestinal resection have not been elucidated. METHODS: Male Wistar rats were fed normal chow or an elemental diet (ED) for 2 weeks. Resected rats underwent 50% jejunectomy or 50% ilectomy. Expired (14)CO(2) levels, following oral administration of (14)C-putrescine were measured in all rats, and compared with the intestinal DAO activity and other mucosal parameters. RESULTS: In the ED group, the (14)CO(2) levels reached a peak earlier, and values were 2.9-fold higher than in the group fed with normal chow. Mucosal alkaline phosphatase (ALP) and DAO activity in the ED group were also higher than in the group fed normal chow, although the mucosal wet weight was significantly lower in the ED group. In the resection groups, all expired (14)CO(2) values increased during measurement. The peak (14)CO(2) values in the jejunectomy group shifted earlier in the postoperative period. The mucosal DAO activity in both the resection groups was higher than it was in the control group at the fifth and 10th postoperative day. However, there were no differences among the three groups at the 15th postoperative day. CONCLUSIONS: Our studies suggested that expired (14)CO(2) after oral administration of (14)C-putrescine correlates with mucosal DAO activity, and that it also reflects intestinal function.     

Effects of amidated gastrin and glycine-extended gastrin on cell proliferation and crypt fission in parenterally and orally fed rats

BACKGROUND/AIMS: It has been suggested that processing variants of gastrin, such as glycine-extended gastrin (G17-Gly), are enterotrophic to the colon. METHODS: Cell proliferation and crypt branching were studied in total parenteral nutrition (TPN) and orally fed rats after infusion of G17-Gly or gastrin-17. RESULTS: Gastrin produced an increase in the weight of the stomach and small intestine and a marked proliferative action on the proximal small intestine, which diminished distally. No proliferative effects of gastrin were seen in the colon. G17-Gly was associated with a small, but significant, increase in colonic weight but had little effect on cell proliferation, except in the gastric fundus. In the distal colon, G17-Gly was associated with a significant decrease in proliferation. Neither agent affected crypt branching in the small intestine or colon, but both proliferation and branching were significantly decreased by TPN. CONCLUSION: Gastrin was trophic to the stomach and the proximal small intestine but not the colon. G17-Gly had only modest proliferative actions on the intestinal epithelium in this study.