To assess correlations between cellular differentiation and enzymatic maturation in the developing rat colon, tissue from fetal, suckling, weanling, and adult rats was analyzed by electron microscopy and assayed for lactase, alkaline phosphatase, and sodium-potassium-stimulated adenosine triphosphatase activities. The proximal and distal colon were analyzed independently at all ages. All three enzymes were detected in the fetal colon when the cells were highly undifferentiated. Postnatally, significant regional differences in cellular ultrastructure appeared, only some of which were directly paralleled by enzymatic changes. Each enzyme had a distinct region-specific developmental pattern. Lactase and sodium-potassium-stimulated adenosine triphosphatase were significantly enhanced at birth, decreasing to adult levels by 15 days postnatal. Regional differences were present, but the patterns were similar. These patterns did not parallel the increase in microvillar height and number and basolateral interdigitations of the surface columnar cells, the structural correlates of lactase, and sodium-potassium-stimulated adenosine triphosphatase, respectively. In contrast, developmental changes in alkaline phosphatase activity paralleled structural maturation, at least in part. The activity levels in the distal colon did not change significantly with age and few major structural changes were noted. In the proximal colon, activity increased markedly after birth, and after 10 days decreased rapidly to adult levels, a pattern that coincided with the transient appearance of villi and specialized cells with apical tubules and vesicles known to have alkaline phosphatase activity. The results show age- and region-related changes in cellular ultrastructure and enzymatic activities, only some of which appear to be directly correlated.

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