The general objectives of the research are to a) characterize the regulation of intestinal calcium absorption and parathyroid hormone secretion during lactation and b) characterize the regulation of synthesis and circulating levels of 1, 25- dihydroxyvitamin D3 during lactation and the neonatal period. Regulation of intestinal calcium absorption will be determined by a) measuring active calcium transport (using everted gut sacs in vitro) and the content of the vitamin D-dependent calcium- binding protein (9 KD CaBP) in the duodenum and ileum of rats during pregnancy and lactation, and b) measuring nonsaturable calcium transport in the jejunum and ileum (with everted gut sacs and Ussing chambers) of lactating rats. Hypotheses to be tested are: (1) duodenal CaBP and active calcium transport in lactation are independent of 1, 25-(OH)2D3 but stimulated by prolactin or another lactation-related hormone, (2) nonsaturable calcium transport in the jejunum and ileum is enhanced during lactation because of lactation-mediated structural changes in the intestinal epithelium. Parathyroid hormone (PTH) secretion will be examined during lactation by determining a) the plasma PTH level by an N-terminal-specific radioimmunoassay (RIA), and b) the rate of release of PTH in vitro from parathyroid cells from lactating rats using an osteosarcoma cell cAMP bioassay for PTH. The potential roles of secretin and corticosterone in enhancing PTH secretion during lactation will be tested by the in vitro PTH release procedure, and the effects of the suckling stimulus and fasting/refeeding will be determined by RIA of plasma PTH. The results may reveal the involvement of factors other than hypocalcemia in maintaining elevated plasma PTH levels during lactation. The control of 1, 25-(OH)2D3 synthesis during lactation and postnatal development will be determined by a renal 25- OHD3-1-hydroxylase assay. Since plasma 1,25-(OH)2D3 in rat pups increases markedly between 2 and 5 weeks of age, while plasma PTH does not change, it is proposed that the rise in plasma 1, 25-(OH)2D3 during this period is due to increasing sensitivity of the renal 25-OHD3-1-hydroxylase enzyme activity to PTH. The proposed work with lactating rats may indicate a role of prolactin in stimulating the renal 25-OHD3-1-hydroxylase. The results of the proposed studies will reveal regulatory factors and adaptive mechanisms that come into play when calcium demands are increased markedly for both the lactating mother and the suckling and newly weaned offspring.
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