Two-step stimulation of intestinal Ca2+ absorption during lactation by long-term prolactin exposure and suckling-induced prolactin surge
Two-step stimulation of intestinal Ca2+ absorption during lactation by long-term prolactin exposure and suckling-induced prolactin surge
复制标题
DOI：
10.1152/ajpendo.00347.2009
复制
发表时间：
2009-09-01
影响因子：
5.1
通讯作者：
Krishnamra, Nateetip
中科院分区：
文献类型：
--
作者：
Charoenphandhu, Narattaphol;Nakkrasae, La-iad;Krishnamra, Nateetip
Charoenphandhu N, Nakkrasae L, Kraidith K, Teerapornpuntakit J, Thongchote K, Thongon N, Krishnamra N.长期泌乳素暴露对哺乳期间肠道Ca2+吸收的影响。[J] .中国生物医学工程学报，2009,31(2):559 - 559。首次发表于2009年6月30日；doi: 10.1152 / ajpendo.00347.2009。-在妊娠和哺乳期，肠道Ca2+吸收增强，为胎儿发育和乳发生提供Ca2+；然而，负责的激素及其机制仍然难以捉摸。我们在此阐明催乳素（PRL）显著刺激怀孕和哺乳期大鼠十二指肠以及Caco-2单层的跨细胞和细胞旁Ca2+转运。具体来说，妊娠期和哺乳期长期暴露于PRL诱导十二指肠细胞在基因组水平上通过上调与跨细胞运输相关的基因（如TRPV5/6和calbinin - d -9k）和细胞旁运输相关的基因（如claudin-3）的表达来适应，从而将Ca2+吸收率提高到一个新的“基线”（步骤1）。在哺乳期间，PRL激增进一步以非基因组方式将Ca2+吸收增加到更高水平（步骤2），以匹配牛奶中Ca2+的损失。prl增强的顶端Ca2+摄取是导致细胞外转运增加的原因，而prl增强的细胞外转运需要claudin-15， claudin-15调节上皮阳离子选择性和细胞外Ca2+运动。这种非基因组PRL作用是由磷酸肌苷3激酶、蛋白激酶C和rhoa相关的卷曲形成线圈的激酶途径介导的。综上所述，肠道Ca2+吸收的两步刺激是由于长期暴露于PRL，导致Ca2+转运蛋白基因上调，提高转运基线，以及哺乳诱导的短暂PRL激增，进一步使Ca2+转运达到最大容量。目前的研究结果还表明，在母乳喂养前15-30分钟补充Ca2+可能对哺乳期母亲最有利，因为更多的Ca2+可以被吸收，作为哺乳诱导的PRL激增的结果。
Charoenphandhu N, Nakkrasae L, Kraidith K, Teerapornpuntakit J, Thongchote K, Thongon N, Krishnamra N. Two-step stimulation of intestinal Ca2+ absorption during lactation by long-term prolactin exposure and suckling-induced prolactin surge. Am J Physiol Endocrinol Metab 297: E609-E619, 2009. First published June 30, 2009; doi: 10.1152/ajpendo.00347.2009.-During pregnancy and lactation, the enhanced intestinal Ca2+ absorption serves to provide Ca2+ for fetal development and lactogenesis; however, the responsible hormone and its mechanisms remain elusive. We elucidated herein that prolactin (PRL) markedly stimulated the transcellular and paracellular Ca2+ transport in the duodenum of pregnant and lactating rats as well as in Caco-2 monolayer in a two-step manner. Specifically, a long-term exposure to PRL in pregnancy and lactation induced an adaptation in duodenal cells at genomic levels by upregulating the expression of genes related to transcellular transport, e. g., TRPV5/6 and calbindin-D-9k, and the paracellular transport, e. g., claudin-3, thereby raising Ca2+ absorption rate to a new "baseline" (Step 1). During suckling, PRL surge further increased Ca2+ absorption to a higher level (Step 2) in a nongenomic manner to match Ca2+ loss in milk. PRL-enhanced apical Ca2+ uptake was responsible for the increased transcellular transport, whereas PRL-enhanced paracellular transport required claudin-15, which regulated epithelial cation selectivity and paracellular Ca2+ movement. Such nongenomic PRL actions were mediated by phosphoinositide 3-kinase, protein kinase C, and RhoA-associated coiled-coil-forming kinase pathways. In conclusion, two-step stimulation of intestinal Ca2+ absorption resulted from long-term PRL exposure, which upregulated Ca2+ transporter genes to elevate the transport baseline, and the suckling-induced transient PRL surge, which further increased Ca2+ transport to the maximal capacity. The present findings also suggested that Ca2+ supplementation at 15-30 min prior to breastfeeding may best benefit the lactating mother, since more Ca2+ could be absorbed as a result of the suckling-induced PRL surge.