Dynamic histology of the antral epithelium in the mouse stomach: V. Proliferation gradient from the gland base to the isthmus at various times of day

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Abstract
The surface epithelium of the mouse pyloric antrum invaginates into blind‐ended tubules whose proliferative activity was investigated by using light microscopy and 3H‐thymidine radioautography. Adult, male, CD1 mice were habituated to 12 hr of light (0600–1800hr) alternating with 12 hr of darkness. Groups of four were given an injection of 40 μCi of 3H‐thymidine per animal and killed 1 hr later at 0600, 1200, 1800, and 2400 hr. The glands at the base of the tubules and the adjacent isthmi were serially cross‐sectioned, and 0.5‐μm‐thick sections were prepared for radioautography. By using morphological criteria, glands were divided into five levels from their base to the isthmus (which was considered as being a sixth level). Proliferative activity was estimated by measuring the proportion of cells incorporating 3H‐thymidine (labeling index) and the proportion of cells undergoing mitosis (mitotic index). The labeling index was found to decrease gradually from a high value in the isthmus to a relatively low one in the gland base; and this was observed at four times of the day. Similar gradients were observed in the mitotic index. Moreover, significant circadian variation was disclosed at most levels by comparing either labeling or mitotic index at four different times of the day. The labeling index tended to peak at the transition from dark to light (0600 hr) and drop at the transition from light to dark (1800 hr). In contrast, mitoses usually reached a maximum at the end of the light cycle (1800 hr) and a minimum at 2400 hr. In summary, the rates of DNA synthesis and cell division showed a sharply decreasing gradient of cell proliferation from the immature cells of the isthmus (level 6) to the mature cells of the gland base (level 1). The existence of some degree of proliferation, even in mature cells, sets apart the renewal taking place in the isthmus‐gland system, since in other renewal sites, cells stop dividing before they reach maturity. Finally, circadian variation has been identified in the proliferative activity of isthmus and gland and appears to be closely related to the light‐dark cycle.