VITAMIN D AND CALCIUM DURING LACTATION

研究的总体目标是a)描述 肠道钙吸收与甲状旁腺的调节 哺乳期荷尔蒙分泌和b)特征 1，25-二氢呋喃的合成和循环水平的调节 哺乳期和新生儿期的双羟基维生素D3。 肠道钙吸收的调节将由以下因素决定 A)测量主动钙转运(使用外翻肠囊 体外)和维生素D依赖的钙含量- 大鼠十二指肠和回肠的结合蛋白(9kD CABP) 在怀孕和哺乳期间，以及b)测量不饱和 空肠和回肠(肠囊外翻)的钙转运 和使用的房间)的哺乳大鼠。有待检验的假设 主要有：(1)十二指肠CABP与哺乳期主动钙转运 不依赖于1，25-(OH)2D3，但受催乳素或 另一种与哺乳有关的激素，(2)不饱和钙 哺乳期间空肠和回肠的转运增强 因为哺乳引起的肠道结构变化 上皮组织。甲状旁腺激素(PTH)分泌将 在哺乳期通过测定a)血浆甲状旁腺素水平进行检查 通过N末端特异性放射免疫分析(RIA)，以及b) 甲状旁腺细胞体外释放甲状旁腺激素的速率 用骨肉瘤细胞cAMP生物测定法测定哺乳大鼠的甲状旁腺素。 促胰液素和皮质酮的潜在作用 将用体外甲状旁腺激素试验检测哺乳期甲状旁腺素的分泌。 释放程序，以及哺乳刺激和 禁食/再喂食将通过血浆甲状旁腺素的RIA来确定。这个 结果可能揭示了除 低钙血症在维持高水平血浆甲状旁腺素水平中的作用 哺乳。哺乳期1，25-(OH)2D3合成的控制 而出生后的发育将由肾脏25决定- OHD3-1-羟基酶测定。大鼠血浆1，25-(OH)2D3 幼崽在2到5周龄之间显著增加，而 血浆甲状旁腺素变化不大，建议血浆升高 1，25-(OH)2D3在此期间是由于对 肾脏25-OHD3-1-羟基酶活性对甲状旁腺激素的影响。这个 拟议的对哺乳期大鼠的研究可能表明催乳素的作用 刺激肾脏25-OHD3-1-羟基酶。结果是 拟议的研究将揭示调节因素和适应性 当钙需求是 哺乳的母亲和哺乳的母亲都显著增加 以及新断奶的后代。

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.