Hormonal regulation of epithelial cell proliferation in the fetal mouse duodenum in vitro

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Abstract
In adult rodents, radioautographic studies have shown that cell proliferation in the small intestinal epithelium is confined to the crypts. However, before birth DNA synthesis occurs also on villi. The role of extrinsic factors in the establishment of the adult pattern of enterocyte proliferation was studied in 17‐day fetal mouse duodenal explants cultured with a completely synthetic medium. The effect of dexamethasone (30 and 300 ng/ml), thyroxine (10 nM), and insulin (125 mU/ml) on labelling indices was determined after 48 hours of culture. At the onset of the culture period close to 60% of the cells located in the first five cell positions in the intervillous areas became labelled after 4 hours of culture in presence of 3H‐thymidine; 8% of the other epithelial cells found higher in the intervillous areas and on villi were also labelled. After 48 hours of culture, well differentiated crypts have developed in all the explants cultured with or without the hormones. The addition of thyroxine or insulin did not modify the labelling indices. However, after 48 hours of culture, the presence of dexamethasone (both concentrations) significantly reduced the labelling index of the cells found over cell position 5 but had no effect on the labelling index of cells located at the bottom of the crypts. When labelling index was determined for each cell position in the crypts at the end of the culture period, it appeared that dexamethasone (300 ng/ml) had no effect thereon for the first five cell positions but had a significant influence on the transitional zone from cell position 6 through 15. In controls, the labelling index fell to 5% for cell position 15, while it reached the same level in position 9 in presence of the hormone. These results indicate that during late fetal life in rodents, glucocorticoids contribute to compartmentalization of the proliferative zone at the bottom of the duodenal crypts and thus might be responsible for the acquisition of the adult proliferative pattern.