VITAMIN D AND CALCIUM IN LACTATING AND SUCKLING RATS

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The long-term objectives of the proposed research are 1) to identify factors and relationships involved in regulation of intestinal calcium absorption and parathyroid hormone secretion during lactation and 2) to determine the effect of vitamin D and weaning on bone matrix and plasma phosphate level in the suckling and newly weaned offspring. Specific aims related to lactating rats include determining a) the relationships between feeding, intestinal hypertrophy-hyperplasia, gastrin secretion and parathyroid hormone (PTH) secretion; b) the effects of corticosterone, secretin and other gastrointestinal hormones on secretion of PTH in vivo and in vitro; c) the relationship between efficiency of intestinal absorption of calcium and lactational intensity, hyperprolactinemia net bone resorption and ionized plasma calcium concentrations in vitamin D-deficient and D-replete lactating rats; and d) the interaction between dietary carbohydrate and vitamin D. Specific aims related to suckling and weaned rat pups include determining the effects of vitamin D and weaning on the plasma phosphate level, bone mineral content and bone collagen crosslink pattern. The proposed studies will utilize previously developed dietary procedures for producing vitamin D-deficient lactating rats and suckling pups, standard methods for radio-immunoassay of parathyroid hormone, corticosterone and gastrin, in vivo and in vitro determination of bone mineral content, calcium absorption determination by net absorption in vivo and with in-situ loops of different intestinal segments, and methods for determining relative amounts and distribution of collagen crosslinks in unmineralized and mineralized bone matrix. The results of these studies should increase our knowledge of physiology and pharmacology of vitamin D and of factors and mechanisms involved in adaptation of calcium metabolism during lactation, as well as mechanisms involved in maturation of bone and mineral metabolism at time of weaning.