首页> 美国卫生研究院文献>Endocrinology >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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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

机译:催乳素在钙稳态中的作用的证据:催乳素对肠道瞬态受体电位6型小肠香草钙吸收和25-羟维生素D31α羟化酶基因的调节

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摘要

Increased calcium transport has been observed in vitamin D-deficient pregnant and lactating rats, indicating that another factor besides 1,25-Dihydroxyvitamin D3 (1,25(OH)2D3) 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)2D3, prolactin, or prolactin + 1,25(OH)2D3. Prolactin alone (1 μg/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-D9k. Combined treatment with 1,25(OH)2D3 and prolactin resulted in an enhancement of the 1,25(OH)2D3 induction of duodenal TRPV6 mRNA, calbindin-D9k mRNA, and an induction of duodenal calcium transport [P < 0.05 compared with 1,25(OH)2D3 alone]. Because lactation is associated with an increase in circulating 1,25(OH)2D3, experiments were done to determine whether prolactin also has a direct effect on induction of 25-hydroxyvitamin D3 1α hydroxylase [1α(OH)ase]. Using AOK B-50 cells cotransfected with the prolactin receptor and the mouse 1α(OH)ase promoter −1651/+22 cooperative effects between prolactin and signal transducer and activator of transcription 5 were observed in the regulation of 1α(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 1α(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)2D3 in induction of intestinal calcium transport genes and intestinal calcium transport, can act as an important modulator of vitamin D-regulated calcium homeostasis.
机译:在缺乏维生素D的怀孕和哺乳期大鼠中观察到钙转运增加,这表明除1,25-二羟基维生素D3(1,25(OH)2D3)以外的其他因素也参与肠道钙转运。为了研究催乳激素作为一种参与钙稳态的激素,向维生素D缺乏症的雄性小鼠注射1,25(OH)2D3,催乳素或催乳素+ 1,25(OH)2D3。单独的催乳激素(终止前48、24和4小时1 g / g体重)可显着诱导十二指肠瞬时受体电位类香草酸6型(TRPV6)mRNA(4倍),但不会引起calbindin-D9k的变化。 1,25(OH)2D3和催乳素的联合治疗导致1,25(OH)2D3诱导十二指肠TRPV6 mRNA,钙结合蛋白-D9k mRNA的诱导和十二指肠钙转运的诱导[P <0.05,与1 ,仅25,(OH)2D3]。由于泌乳与循环中1,25(OH)2D 3 的增加有关,因此进行了实验以确定催乳素是否也对25-羟基维生素D 3的诱导有直接影响。 sub>1α羟化酶[1α(OH)ase]。使用与泌乳素受体和小鼠1α(OH)酶启动子-1651 / + 22共转染的AOK B-50细胞,在1α(OH)酶的调节中观察到了催乳素与信号转导子和转录激活子5之间的协同作用。另外,在经催乳素受体转染的AOK B-50细胞中,通过蛋白质印迹分析确定,催乳素处理(400 ng / ml)以及信号转导和转录激活因子5可显着诱导1α(OH)ase蛋白。因此,催乳素通过多种机制,包括调节维生素D代谢,诱导TRPV6 mRNA以及与1,25(OH) 2 D 3 协同作用来诱导肠道钙转运基因和肠道钙转运,可以作为维生素D调节钙稳态的重要调节剂。

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