VITAMIN D AND CALCIUM DURING PREGNANCY AND LACTATION

本项目的长期目标是阐明 参与钙（Ca）代谢对增加的Ca的适应 生殖需求和新生儿期。 过去的结果已经 循环浓度变化的模拟临床研究 的钙调节激素在哺乳期妇女，以及研究 极低出生体重儿肠道钙吸收研究 未来的研究 也应该同样具有煽动性。 条例的具体目标 肠道钙吸收在生殖过程中，包括鉴定 围产期十二指肠活性钙峰值的原因 大鼠妊娠20天至哺乳期第4天之间的转运。 的 1，25-（OH）2D3、催乳素、胎盘催乳素-II、雌激素的潜在作用， 或甲状旁腺相关肽（PTHrP）将通过改变 孕鼠血清中这些激素的水平。 案件的变化 转运比（浆膜/粘膜，使用外翻肠囊）， 十二指肠钙结合蛋白-D9k及其信使RNA的浓度，以及 将测量十二指肠1，25-（OH）2D3受体。 非饱和Ca 在空肠和回肠中的吸收将在 围产期，为了延长我们的早期工作， 提高泌乳后期非饱和钙吸收效率。 关于调节甲状旁腺激素（PTH）分泌的具体目的 在哺乳期将包括阐明为什么超生理血清钙 水平不抑制泌乳大鼠血清PTH水平相同 程度与非哺乳期大鼠相同。 骨细胞CAMP生物测定将用于 探讨钙抑制大鼠PTH释放的方式 甲状旁腺细胞，并确定是否有一个独特的（关系 泌乳期细胞外和细胞内钙浓度之间的关系 大鼠，也许是由于皮质酮的作用，它在高循环 哺乳期的水平。 关于管制药物合成的具体目标 哺乳期和哺乳期大鼠中的1，25-（OH）2D3，包括确定 在妊娠结束时循环1，25-（OH）2D3水平的下降， 1-2泌乳天数的平行变化所造成的肾 激素的生物合成，如由肾细胞的活性所确定的。 25-OHD-1-OH酶，如果妊娠相关的增加可能是由于 低钙血症、PTH、胎盘催乳素-II或雌激素对1 - OHD-1-OH酶，或胎盘25-OHD-1-OH酶升高， 甲状旁腺素相关肽（PTHrP）刺激。 实验 还将揭示1，25-（OH）2D3的肾外合成是否发生在 泌乳，可能是乳腺对旁分泌作用的反应 的PTHRP。

The long-term objectives of this project are to elucidate the mechanisms involved in the adaptation of calcium (Ca) metabolism to the increased Ca demands of reproduction and the neonatal period. Past results have already stimulated clinical studies on the changes in the circulating concentration of the Ca regulating hormones in lactating women, as well as studies on intestinal Ca absorption in very low-birthweight infants. Future studies should be similarly provocative. Specific aims concerning the regulation of intestinal Ca absorption during reproduction include the identification of factors responsible for the periparturient peak of duodenal active Ca transport between 20 days of pregnancy and day 4 of lactation in rats. The potential role of 1,25-(OH)2D3, prolactin, placental lactogen-II, estrogen, or parathyroid hormone-related peptide (PTHrP) will be evaluated by varying the serum levels of these hormones in pregnant rats. Changes in the Ca transport ratio (serosal/mucosal, using everted gut sacs), the concentration of duodenal calbindin-D9k and its messenger RNA, and the duodenal 1,25-(OH)2D3 receptor will be measured. Nonsaturable Ca absorption in the jejunum and ileum will be determined during the periparturient period, in order to extend our earlier work indicating enhanced efficiency of nonsaturable calcium absorption in late lactation. Specific aims regarding regulation of parathyroid hormone (PTH) secretion during lactation will include elucidating why superphysiolgic serum Ca levels do not suppress serum PTH levels of lactating rats to the same extent as in nonlactating rats. A bone cell CAMP bioassay will be used to study the pattern of Ca suppression of PTH release from dispersed rat parathyroid cells, and to determine if there is a unique (relationship between extracellular and intracellular Ca concentrations in lactating rats, perhaps due to an action of corticosterone, which circulates at high levels during lactation. Specific aims on regulation of synthesis of 1,25-(OH)2D3 in lactating and suckling rats include determining if the rise in circulating 1,25-(OH)2D3 levels at the end of pregnancy and the fall at 1-2 days of lactation are caused by parallel changes the rate of renal biosynthesis of the hormone as determined by the activity of the renal 25-OHD-1-OHase, and if the pregnancy-related increase could be due to an effect of hypocalcemia, PTH, placental lactogen-II or estrogen on the 1 -OHase, or to an increase in placental 25-OHD-1-OHase that may be stimulated by parathyroid hormone-related peptide (PTHrP). Experiments will also reveal if extrarenal synthesis of 1,25-(OH)2D3 occurs in lactation, perhaps by the mammary gland in response to a paracrine action of PTHRP.