Evidence for a Role of Prolactin in Calcium Homeostasis: Regulation of Intestinal Transient Receptor Potential Vanilloid Type 6, Intestinal Calcium Absorption, and the 25-Hydroxyvitamin D3 1α Hydroxylase Gene by Prolactin
Evidence for a Role of Prolactin in Calcium Homeostasis: Regulation of Intestinal Transient Receptor Potential Vanilloid Type 6, Intestinal Calcium Absorption, and the 25-Hydroxyvitamin D3 1α Hydroxylase Gene by Prolactin
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DOI：
10.1210/en.2010-0033
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发表时间：
2010-07-01
期刊：
影响因子：
4.8
通讯作者：
Christakos, Sylvia
中科院分区：
文献类型：
--
作者：
Ajibade, Dare V.;Dhawan, Puneet;Christakos, Sylvia
在维生素D缺乏的孕鼠和哺乳期大鼠中观察到钙转运增加，表明除1，25(OH)(2)D-3(1，25(OH)(2)D-3)外，另一种因素参与了肠道钙转运。为了研究催乳素作为一种激素参与钙稳态，维生素D缺乏的雄性小鼠被注射1，25(OH)(2)D-3，催乳素，或催乳素+1，25(OH)(2)D-3。单用催乳素(1ug/g体重，终止前48、24和4h)可显著诱导十二指肠瞬时受体电位香草样物质6型(TRPV6)mRNA表达(4倍)，但对Calbindin-D-9k无明显影响。联合应用1，25(OH)(2)D-3和催乳素可增强1，25(OH)(2)D-3对十二指肠TRPV6、Calbindin-D9k mRNA的诱导作用，并诱导十二指肠钙转运[P<；0.05与1，25(OH)(2)D-3单独作用相比]。由于哺乳与循环中1，25(OH)(2)D-3的增加有关，因此进行了实验以确定催乳素是否也直接影响25-羟基维生素D-3α羟基酶[1α(OH)酶]的诱导。用共转催乳素受体和小鼠1α(OH)酶启动子-1651/+22的AOK B-50细胞观察到催乳素与信号转导和转录激活因子5在1α(OH)酶调控中的协同作用。此外，在转导催乳素受体的AOK B-50细胞中，经催乳素(400 ng/ml)和信号转导及转录激活子5处理后，Western印迹分析显示1α(OH)酶蛋白的表达显著增加。因此，催乳素通过调节维生素D代谢、诱导TRPV6mRNA、与1，25(OH)(2)D-3协同诱导肠道钙转运基因和肠道钙转运等多种机制，可作为维生素D调节的钙稳态的重要调节剂。(内分泌学151：2974-2984,2010)
Increased calcium transport has been observed in vitamin D-deficient pregnant and lactating rats, indicating that another factor besides 1,25-Dihydroxyvitamin D-3 (1,25(OH)(2)D-3) is involved in intestinal calcium transport. To investigate prolactin as a hormone involved in calcium homeostasis, vitamin D-deficient male mice were injected with 1,25(OH)(2)D-3, prolactin, or prolactin + 1,25(OH)(2)D-3. Prolactin alone (1 mu g/g body weight 48, 24, and 4 h before termination) significantly induced duodenal transient receptor potential vanilloid type 6 (TRPV6) mRNA (4-fold) but caused no change in calbindin-D-9k. Combined treatment with 1,25(OH)(2)D-3 and prolactin resulted in an enhancement of the 1,25(OH)(2)D-3 induction of duodenal TRPV6 mRNA, calbindin-D9k mRNA, and an induction of duodenal calcium transport [P < 0.05 compared with 1,25(OH)(2)D-3 alone]. Because lactation is associated with an increase in circulating 1,25(OH)(2)D-3, experiments were done to determine whether prolactin also has a direct effect on induction of 25-hydroxyvitamin D-3 1 alpha hydroxylase [1 alpha(OH)ase]. Using AOK B-50 cells cotransfected with the prolactin receptor and the mouse 1 alpha(OH)ase promoter -1651/+22 cooperative effects between prolactin and signal transducer and activator of transcription 5 were observed in the regulation of 1 alpha(OH) ase. In addition, in prolactin receptor transfected AOK B-50 cells, prolactin treatment (400 ng/ml) and signal transducer and activator of transcription 5 significantly induced 1 alpha(OH)ase protein as determined by Western blot analysis. Thus, prolactin, by multiple mechanisms, including regulation of vitamin D metabolism, induction of TRPV6 mRNA, and cooperation with 1,25(OH)(2)D-3 in induction of intestinal calcium transport genes and intestinal calcium transport, can act as an important modulator of vitamin D-regulated calcium homeostasis. (Endocrinology 151: 2974-2984, 2010)