Investigation of mechanisms relating to the maturational events of rat enteric (small intestine) epithelium form the basis of this research proposal. Ontogenic maturational processes of rat enteric epithelium culminate abruptly in dramatic cytokinetic, structural and functional changes, which occur as coordianted time-related events which accompany dietary changes with weaning. The following studies will examine regulatory factors relating to these maturational events generally and to the changes in disaccharidases in particular. Specific hypothesis and questions to be tested are listed. a) Mechanism of rapid lactase decline accompanying weaning. Hypothesis to be tested: cytokinetic changes leading to shortened enterocyte life-span serve as the causal basis of the well-recognized yet unexplained general phenomenon of rapid enteric lactase decline accompanying weaning of the suckling mammal. B) Role of dietary and humoral factors. Hypothesis to be tested: nutrition, both qualitative and quantitative, and humoral agents serve to regulate enteric disaccharidase levels by altering their synthesis rates and/or the survival-span of the enterocyte. c) Mechanisms relating to transitional changes in disaccharidase distribution patterns along the length of the developing small intestine. Hypothesis to be tested: maturational changes in enteric structure and function preceding weaning do not occur uniformally along thelength of the intestine. d) Relationship between the functional development and surface dimensions of the microvillus membrane. Question to be tested: is the functional development of the microvillus membrane accompanied by changes in its surface dimension? e) Synthesis of disaccharidases in relation to their membrane composition. Question to be tested: Are the synthesis rates of the disaccharidases sucrase, maltase and lactase proportional to their relative presence on themicrovillus membrane?
