Sprague-Dawley rats that had been subjected 2 months previously to partial resection (10 per cent) of thc small intestine and an equal number of control rats were injected with tritiated thymidine and sacrificcd at intervals during the subsequent 16 hours. Segments of duodenum, jejunum and ileum were prestained by the Feulgen technique and radioautographed. ~fhe proportion of crypt cells bearing labeled nuclei, the perccntage of labeled crypt cells in mitosis and the appearance of labeled crypt ceils on the villi were determined. Comparison of control and resected rats showed that (a) the proportion of intestinal crypt cells incorporating thymidine was considerably greater and uniformly high throughout the shortened intestinc, (b) the life cycle of crypt cells was slightly reduced, and was uniform throughout the shortened intestine, and (c) the time during which cells wcre retained in crypts was markedly reduced. On the basis of persistent, generalized increase in the production of crypt cells, and on prior evidence that the epithelial cells of shortened intestine continue to have a brief life span and evidence of metabolic immaturity, the existence of a humoral factor, tentatively called "intestinal epithelial growth hormone," is postulated.As reported previously (1), resection of I0 per cent of the small intestine (removal of 10 cm of ileum) in rats was followed by a pronounced increase in the rate of migration of the epithelial cells covering the villi in the remaining portion of small intestine. Two months after resection, the distance traveled by mucosal cells examined 2 and 24 hours after labeling with tritiated thymidine was increased by approximately 23 per cent in the duodenum, 114 per cent in the jejunum, and 141 per cent in the ileum. The "life span" of epithelial cells in the intestinal mucosa, as estimated from the rate of migration and the height of villi, was decreased to 82, 46, and 42 per cent of normal for duodenum, jejunum, and ileum, respectively.The present study demonstrates that the rate of appearance of new ceils on the intestinal villi is accelerated in proportion to the increased rate of cell migration. Proliferation in intestinal crypts is also increased throughout the small intestine, but this increase is not proportional to the increase in the rate of migration. It is proposed that a growth factor, provisionally called intestinal epithelial growth hormone (IEGH), is released in response to intestinal resection and that this factor accelerates the rate of epithelial proliferation throughout the small bowel.
M A T E R I A L S AND M E T H O D SIn a first experiment, the experimental animals consisted of 16 male Sprague-Dawley rats, weighing 300 to 350 gin. A 10 cm portion of the lower ileum, representing 10 per cent of the length of the small intestine, was removed from each at a point about 20 cm 285 on