MATERNAL GROWTH FACTORS IN NEONATAL GROWTH

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Recent evidence in the literature indicates that the milk of lactating mammals contains polypeptide growth factors which are capable of stimulating the proliferation of animal cells in vitro. The presence of relatively high concentrations of mitogenic activities in mammary secretions raises a number of important questions with regard to their identify, structure, synthesis, secretion and possible involvement in the early development of the neonate. The aim of this proposal is to use the domestic pig, Sus domesticus, for an examination of growth promoting activities in mammary secretions and their biological effects in the newborn animal. The pig was chosen for these experiments since it undergoes marked physiological changes early in life, many of which are clearly dependent on the suckling process. For example, early growth and maturation of the intestinal epithelium in the newborn pig is dependent upon epithelial cell proliferation, perhaps stimulated in part by ingested factors. In addition, large amounts of colostrum can be obtained from lactating animals and will serve as the starting material for growth factor isolation. Virtually nothing is known at present concerning the nature of growth promoting activities in porcine mammary secretions. Therefore, initial experiments will attempt to identify and characterize these mitogenic activities. In turn, an appropriate immunological or receptor based assay will be developed for measurement of the factor in mammary secretions and maternal tissues. Once the nature of these polypeptides is established, then attempts will be made to isolate and characterize their corresponding gene(s) using recombinant DNA techniques. The temporal and tissue-specific patterns of expression of the gene will also be determined for both maternal and neonatal sources. The final aspect of the study will involve cloning of the gene in a bovine papilloma virus-derived vector followed by transfection into murine C127 cells. This experiment should result in the production of relatively large quantities of the factor in cell culture. This material will then be utilized for physiological studies in the neonate. It is hoped that a study of growth promoting activities in mammary secretions will contribute towards a further understanding of what the roles of polypeptide growth factors are in vivo and how their expression relates to early postnatal growth. These studies should have a direct relevance to human infant nutrition.