VITAMIN D AND CALCIUM DURING PREGNANCY AND LACTATION

这个项目的长期目标是阐明这些机制。 参与钙(Ca)代谢对钙增加的适应 生殖需求和新生儿期。过去的结果已经 循环血药浓度变化的模拟临床研究 哺乳妇女体内钙调节激素的研究进展 极低出生体重儿的肠道钙吸收。未来研究 应该同样具有挑衅性。关于该条例的具体目标 生殖过程中肠道钙吸收的研究包括鉴定 十二指肠活动性病例围产期高峰期相关因素分析 大鼠妊娠20天至哺乳期第4天之间的转运。这个 1，25-(OH)2D3，催乳素，胎盘催乳素-II，雌激素， 或甲状旁腺激素相关肽(PTHrP)将通过改变 妊娠大鼠血清中这些激素的水平。案例中的变化 转运比率(浆膜/粘膜，使用外翻的肠囊)， 十二指肠钙结合蛋白-D9k及其信使RNA的浓度，以及 测定十二指肠1，25-(OH)2D3受体。不可饱和的情况 空肠和回肠的吸收将在 围产期，为了延续我们前期的工作表明 提高哺乳后期非饱和钙吸收效率。 甲状旁腺激素(PTH)分泌调控的特殊靶点 在哺乳期间将包括阐明为什么超生理活性血清 水平不会将哺乳期大鼠的血清甲状旁腺素水平抑制到同样的水平 程度与非哺乳期大鼠相同。骨细胞cAMP生物测定将用于 钙抑制分散大鼠甲状旁腺素释放规律的研究 甲状旁腺细胞，并确定是否存在唯一的(关系 哺乳过程中细胞外和细胞内钙浓度之间的关系 老鼠，可能是由于皮质酮的作用，皮质酮在高循环 哺乳期间的水平。关于调节合成的具体目的 在哺乳期和哺乳期大鼠的1，25-(OH)2D3包括确定是否升高 妊娠末期循环中1，25-(OH)2D3水平 哺乳期的1-2天是由肾脏的平行变化引起的 由肾脏活动决定的激素的生物合成 25-OHD-1-OHase，如果怀孕相关的增加可能是由于 低钙血症、甲状旁腺激素、胎盘催乳素-II或雌激素对1 -OHase，或胎盘25-OHD-1-OHase的增加可能是 甲状旁腺激素相关肽(PTHrP)刺激。实验 也将揭示肾外合成1，25-(OH)2D3是否发生在 哺乳，可能是乳腺对旁分泌作用的反应 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.