ROLE OF MILK-BORNE SUBSTANCES IN DEVELOPING LIVER

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The overall aim of this study is to elucidate structural and functional differences in the development of the microvasculature and its surrounding parenchyma and cells in livers of suckling rats that may be attributed to the presence of hormones or hormone-like substances in breast milk. This is being accomplished using high resolution in vivo microscopic methods as well as light and electron microscopic morphometry of histologic, immunohistochemical, and in situ hybridization preparations. More specifically, the following parameters will be studied as a function of the presence or absence in an artificial milk diet of growth factors alone or in combination, e.g., epidermal growth factor (EGF), prolactin, and insulin-like growth factors (IGF I and II), which are transported biologically intact to the liver of suckling rats: (a) development of the hepatic microvascular system including patterns and rates of blood flow, dimensional changes in diameters, lengths and separation of vessels and reactivity to the test substances; (b) development of sinusoid wall structure including cellular composition as well as heterogeneity and function; (c) development of hepatic parenchymal cell organization into adult cell plates as reflected by DNA synthetic index, mitotic index, appearance of binucleated cells and structural heterogeneity; (d) development of functional heterogeneity for glucose metabolism in hepatic parenchymal cells as reflected in the expression of mRNA for the periportal enzyme, glucose-6-phosphatase G-6-Pase, and the centrilobular enzyme, glucokinase (GK), demonstrated by in situ hybridization. The results should help to elucidate the role(s) of these substances in affecting postnatal liver development during the suckling period. The results also ultimately may be useful in establishing the rationals for inclusion of some of these substances in proprietary infant milk formulas.