Influence of starvation and refeeding on mucosal size and epithelial renewal in the rat small intestine

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 30–40% 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.