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1,25-二羟胆钙化醇介导的钙吸收和基因表达在雌性小鼠中高于雄性小鼠。

1,25 dihydroxycholecalciferol-mediated calcium absorption and gene expression are higher in female than in male mice.

作者信息

Song Yurong, Fleet James C

机构信息

Department of Foods and Nutrition and the Interdepartmental Nutrition Program, Purdue University, West Lafayette, IN 47907, USA.

出版信息

J Nutr. 2004 Aug;134(8):1857-61. doi: 10.1093/jn/134.8.1857.

DOI:10.1093/jn/134.8.1857
PMID:15284366
Abstract

Recent advances in bone and calcium (Ca) metabolism have relied upon genetically modified mice. However, although human studies have identified gender as an important modulator of Ca metabolism, its effect on Ca metabolism has not been examined in mice. Here we examined basal and vitamin D-regulated Ca absorption (in situ ligated loops) and mRNA levels for the apical membrane calcium channel, TRPV6, and the calcium binding protein, calbindin D(9k) (CaBP) mRNA levels (real-time PCR) in duodenum of female and male mice. At 2 mo of age, females fed a 5 g Ca/kg diet had higher Ca absorption (62.3 +/- 4.8 vs. 47 +/- 3.6%) and TRPV6 mRNA levels than males even though plasma 1,25 dihydroxyvitamin D [1,25(OH)(2) D] was not different. In mice fed high (20 g/kg), normal (5 g/kg), or low (0.2 g/kg) Ca diets for 7 d to alter plasma 1,25(OH)(2) D (91 +/- 12, 322 +/- 25, and 587 +/- 43 pmol/L, respectively), the relation between Ca absorption (slope = 0.116 vs. 0.084, P = 0.021) or duodenum TRPV6 mRNA (slope = 0.042 vs. 0.025, P = 0.034) and circulating 1,25(OH)(2) D was steeper in females. After a single 1,25(OH)(2) D injection (200 ng/100 g body weight), peak induction of TRPV6 mRNA was 2-fold greater (at 6 h) and CaBP mRNA was 20% higher in females (at 16 h). Duodenal vitamin D receptor mRNA levels did not differ between genders. Our data indicate that female mice are more sensitive to changes in serum 1,25(OH)(2) D levels than males and that this must be considered when using mice to study calcium and bone biology.

摘要

骨骼与钙(Ca)代谢领域的最新进展依赖于基因工程改造的小鼠。然而,尽管人体研究已确定性别是钙代谢的重要调节因素,但尚未在小鼠中研究其对钙代谢的影响。在此,我们检测了雌性和雄性小鼠十二指肠中基础状态下以及维生素D调节的钙吸收(原位结扎肠袢法),以及顶端膜钙通道TRPV6和钙结合蛋白钙结合蛋白D(9k)(CaBP)的mRNA水平(实时定量PCR)。在2月龄时,即使血浆1,25-二羟维生素D [1,25(OH)₂D] 水平无差异,但喂食5 g Ca/kg饮食的雌性小鼠的钙吸收(62.3±4.8% 对47±3.6%)和TRPV6 mRNA水平高于雄性小鼠。在分别喂食高钙(20 g/kg)、正常钙(5 g/kg)或低钙(0.2 g/kg)饮食7天以改变血浆1,25(OH)₂D水平(分别为91±12、322±25和587±43 pmol/L)的小鼠中,雌性小鼠的钙吸收(斜率 = 0.116对0.084,P = 0.021)或十二指肠TRPV6 mRNA(斜率 = 0.042对0.025,P = 0.034)与循环1,25(OH)₂D之间的关系更为显著。单次注射1,25(OH)₂D(200 ng/100 g体重)后,雌性小鼠TRPV6 mRNA的峰值诱导(6小时时)高2倍,CaBP mRNA(16小时时)高20%。十二指肠维生素D受体mRNA水平在两性之间无差异。我们的数据表明,雌性小鼠对血清1,25(OH)₂D水平变化比雄性小鼠更敏感,在利用小鼠研究钙和骨骼生物学时必须考虑这一点。

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