As an index of villus size, the number of epithelial cells per representative villus section was counted in longitudinal sections of the rat small intestine. Villus size was found to decrease gradually along the length of the small intestine, with villi being nearly three times as large in upper duodenum as in terminal ileum. The influence of various surgical operations on villus size was then examined. In ileal segments inserted into the jejunum, villi enlarged to the size of local jejunal villi. In jejunal segments inserted into the ileum, villi decreased almost to the size of local ileal villi. Thus, villus size was influenced by the environment, that is, most probably by the different types of chyme in jejunum and ileum.In duodenal segments inserted into the ileum, villi did not decrease in size, and distally located ileal villi enlarged. This and other experiments indicated that the duodenum produced secretions which not only neutralized the villus-reducing effect of the ileal environment, but also exerted a potent villus-enlarging effect. Pyloric secretions had a similar villus-enlarging effect.Segments of intestine were made into blind sacs by closing their proximal end and joining their distal end to the colon, so as to remove the influence of the chyme. Villus size decreased in sacs of jejunum and lower duodenum (without the duodenal papilla), but increased in sacs of ileum. Thus in the three types of sacs, there was a tendency for villi to acquire an intermediate size.In conclusion, a n intermediate villus size, which is postulated to exist in chyme-free, non-functional intestine, would normally be modified by two types of factors: villusenlarging factors present mainly in pyloric and duodenal secretions, and villus-reducing factors present in the ileal chyme. Interaction between these factors would result in the gradient of villus size along the small intestine.In the small intestine of the rat, villi exhibit a gradual decrease in size from the upper duodenum to the terminal ileum, as may be seen in figures 1-5 (Altmann and Enesco, '67). Since villi have a rapidly renewing component, the epithelium, the constancy of their pattern must be maintained in each region by proper regulatory mechanisms. The aim of the present work was to find out what type of factors were involved in the mechanisms controlling villus size and, in particular, whether these factors were intrinsic to the tissue or provided by the environment. The approach used was to separate intestinal segments by surgical procedures and to transpose them to other gastro-intestinal areas. In some cases, the segments were inserted in different locations, but within the intestinal continuity; the villi were thus exposed to a different intestinal content, since the content varies from fluid gastric chyme in the duodenum to semisolid fecal material in AM. J. ANAT., 127: 15-36. the terminal ileum. In other cases, segments were made to open as blind sacs onto the side of ileum or colon, thus becoming largely non-functional as well as empty of ...

Adult male rats were fasted for 0 (controls), three, five and seven days; a group was refed for one day after six days of starvation. Histological samples were taken from five regions along the length of the small intestine. The sizes of the villi, crypts and mitotic pool were estimated by measuring the number of epithelial cells per villus and crypt section and the number of mitotic figures per crypt section. Additional studies were carried out using colchicine for estimating mitotic time and methotrexate for inhibiting mitosis.All three parameters decreased progressively during starvation; the decrease in villus size was most pronounced in the duodenum and gradually less distalward. Refeeding increased the mitotic pool in every region; crypt size did not increase and villus size increased slightly in duodenum and jejunum only. When refeeding was combined with mitotic inhibition, the cell population of the crypts became depleted by 3 0 4 0 % without change in villus size; thus, renewal appeared to continue by crypt cells migrating to the villi.Mitosis in the crypts is used for epithelial renewal in the adult intestine. The calculated turnover time of the epithelium was longer than normal and similar in every stage of starvation. Refeeding appeared to stimulate renewal. Since villus size changed somewhat independently from mitotic activity, the involvement of a separate mechanism controlling villus size was indicated.Mucosal size is determined mainly by the size of the crypts and the villi in the small intestine. The size of these structures and the size of the mitotic pool in the crypts were measured in the present work in starved and refed rats.In accordance with previous works (Altmann, '67; Altmann and Leblond, '70; Altmann, '71), the number of epithelial cells present in the villi and the crypts was used as an index of villus size and crypt size, respectively. These indices combined with the data on mitosis provided some information on the rate of epithelial renewal.The same previous works have provided evidence that various intestinal secretions present in the intestinal chyme influence villus size, crypt size and, to a certain extent, epithelial renewal. The purpose of the present work was to extend these studies to the investigation of the effects of food.AM. J. ANAT., 133: 391-400. MATERIALS AND METHODSAnimal techniques. Adult male Wistar rats weighing about 310 gm were used. Groups of five animals were fasted for 0 (controls), three, five and seven days. Water was freely available. A group of five rats was fasted for six days and then refed with Purina Laboratory Chow for one day. Another group of three rats was refed similarly but with powdered Purina Laboratory Chow which contained 0.25 mg methotrexate per gm. Finally, each of six additional animals were injected subcutaneously with 0.3 mg of colchicine three hours before sacrifice; three of these animals were maintained on normal diet and three of them were fasted for seven days prior to sacrifice.The animals were killed between 9 AM and 11 A...

Along the rat small intestine, the size of the villi gradually decreases from a maximum in the duodenum to less than half of this size in the terminal ileum. In previous work, various villus enlarging and reducing factors present in the intestinal chyme were found to control villus size. A villus enlarging factor which appeared to reach the intestine through the duodenal papilla was presently investigated.Transplants of duodenal papilla, together with a small segment of the duodenum, were made to isolated ileal segments and to the lower ileum. At both sites, the transplants elicited a marked villus enlargement within a month. A previous finding was that villus size decreased in isolated duodenal segments unless the duodenal papilla was present.In the next experiments, the bile-drainage was diverted from the duodenal papilla by implanting the bile duct into an isolated ileal segment which in turn was joined to the colon. The duodenal papilla which now transmitted only pancreatic secretions was then transplanted to the ileum. The bile caused only moderate villus enlargement in the ileal segments whereas marked villus enlargement took place in the ileum receiving the pancreatic secretions.It was concluded that a villus enlarging influence reached the intestine through the duodenal papilla. The pancreatic secretions appeared to play a major role in this influence.In the rat, the size of the intestinal villi decreases gradually from the duodenum toward the ileum so that the villi in the lower ileum are less than half the size of the duodenal villi (Altmann and Enesco, '67; Clarke, '70). In previous work, these regional differences in villus size were attributed largely to effects originating from the secretions and other materials making up the intestinal chyme (Altmann and Leblond, '70). Thus, secretions of the stomach and the duodenum were shown to contain villus enlarging factors whereas the ileal chyme appeared to contain villus reducing factors. Furthermore, there was evidence that the secretions reaching the intestine through the duodenal papilla also contained villus enlarging factors. The purpose of the present work was to confirm this latter observation and to find out whether the bile or the pancreatic secretions were involved. The method of approach was to transplant the duodenal AM. J. ANAT., 132: 167-178.papilla and the associated ducts into the ileum and also into isolated segments of the ileum. The influence of these transplants on villus size was then quantified.Male Wistar rats weighing 300-320 gm were used. The various procedures will now be described while the outline of the various experiments will be given in the Observations.Six control animals were maintained under normal laboratory conditions. They were provided with Purina Laboratory Chow and tap water ad libitum. Four additional animals received a semisynthetic diet instead of the Purina pellets. This diet contained 10% casein, 20% lactalbumin hydrolysate, 42% dextrose, 10% sucrose, 9% a mixture of vitamins, salt and yeast, 2% corn oi...

In the ascending colon of adult male rats, large accumulations of differentiated, mucous-type cells were observed which formed the deep one-half to one-third of the crypts almost exclusively. Mitotic activity was localized to the midcrypt, to columnar-type cells. The mucous-type cells were designated as "deep crypt secretory" (DCS), and their histological study was initiated. In the light microscope, the apical cytoplasm was distended with mucous vacuoles which stained differently from goblet cells after using periodic acid-Schiff (PAS), alcian blue, or a Masson stain. In electron-micrographs, a well-developed Golgi complex and rough edoplasmic reticulum in addition to a large number of electron-opaque vacuoles indicated active production of a glycoprotein. The midcrypt mitotic activity was further demonstrated by using the colchicine technique and 3H-thymidine radioautography. A gradual increase of mucus content and a decrease of nuclear and nucleolar size in the DCS cells from midcrypt to crypt base indicated that these cells originate in midcrypt and mature as they progress toward the crypt base. Cell counts showed that the number of cells constituting the crypts was about the same all along the colon, but the percentage of DCS cells varied: 33% in ascending and 21% in transverse colon. Only 5% and 8% deep-crypt mucous-type cells were found in descending colon and cecum, respectively; but these cells differed in appearance from the mature DCS cells. In conclusion, the presence of a large number of nonmitotic end cells with intense secretory activity has been ascertained for the deep crypts of the ascending colon. The exact relation of these cells to the vacuolated or other epithelial cell types remains for further study.