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甲状旁腺激素可增加维生素D缺乏雌性大鼠的骨形成并改善矿物质平衡。

Parathyroid hormone increases bone formation and improves mineral balance in vitamin D-deficient female rats.

作者信息

Toromanoff A, Ammann P, Mosekilde L, Thomsen J S, Riond J L

机构信息

University of Zurich, Institute of Animal Nutrition, Switzerland.

出版信息

Endocrinology. 1997 Jun;138(6):2449-57. doi: 10.1210/endo.138.6.5193.

Abstract

The present study was designed to investigate whether enhanced bone formation due to intermittent PTH administration is dependent on vitamin D metabolites. Forty-eight female Sprague-Dawley rats were randomized into four groups: 1) vitamin D-sufficient, saline-injected (+D Sal); 2) vitamin D-sufficient, human (h) PTH-(1-38)-treated (+D PTH); 3) vitamin D-deficient, saline-injected (-D Sal); and 4) vitamin D-deficient, hPTH-(1-38)-treated (-D PTH) animals. The -D diet contained 2% calcium (Ca), 1.25% phosphorus (P), and 20% lactose to maintain normocalcemia and normophosphatemia despite vitamin D deficiency. The +D diet contained 0.8% Ca, 0.5% P, 20% lactose, and 1000 IU/kg vitamin D. After 45 days of either diet, the rats were injected with 50 microg/kg BW PTH or saline, s.c., daily for 2 weeks. Serum Ca, Mg, P, albumin, and creatinine were similar in all groups. PTH administration decreased endogenous PTH concentrations in the -D PTH compared with those in the - D Sal group. Serum alkaline phosphatase activity, bone mass measurements, dual energy x-ray absortiometric analysis of mineral density, and mechanical testing values in vertebrae and femora of the -D Sal animals did not significantly differ from those in +D Sal animals. Moreover, in both diet groups, PTH improved bone biochemical activity (as assessed by serum alkaline phosphatase), bone mass, mineral density, and biomechanical properties. These results indicate that mineral supply, more than vitamin D itself, may be important for normal bone mineralization and to enable PTH to enhance bone formation. A balance study performed during the last 3 days of the experiment revealed that PTH increased apparent intestinal magnesium absorption in the +D group only. Ca and P retention, however, were augmented in both diet groups after PTH treatment. In conclusion, in normocalcemic and normophosphatemic -D rats, PTH treatment reduced the increased endogenous hormone concentration and improved Ca and P retention. Furthermore, PTH may have a vitamin D-dependent influence on intestinal magnesium absorption. Finally, short term PTH treatment is anabolic in bone of vitamin D-deficient rats when adequate mineral amounts are provided in the diet.

摘要

本研究旨在调查间歇性给予甲状旁腺激素(PTH)所导致的骨形成增强是否依赖于维生素D代谢产物。48只雌性斯普拉格-道利大鼠被随机分为四组:1)维生素D充足,注射生理盐水(+D Sal);2)维生素D充足,用人甲状旁腺激素(1-38)治疗(+D PTH);3)维生素D缺乏,注射生理盐水(-D Sal);4)维生素D缺乏,用人甲状旁腺激素(1-38)治疗(-D PTH)的动物。-D饮食含有2%钙(Ca)、1.25%磷(P)和20%乳糖,以维持正常血钙和血磷水平,尽管存在维生素D缺乏。+D饮食含有0.8% Ca、0.5% P、20%乳糖和1000 IU/kg维生素D。在两种饮食喂养45天后,大鼠皮下注射50μg/kg体重的PTH或生理盐水,每日一次,持续2周。所有组的血清钙、镁、磷、白蛋白和肌酐相似。与-D Sal组相比,给予PTH降低了-D PTH组的内源性PTH浓度。-D Sal动物的血清碱性磷酸酶活性、骨量测量、双能X线吸收法测定的矿物质密度以及椎骨和股骨的力学测试值与+D Sal动物相比无显著差异。此外,在两个饮食组中,PTH均改善了骨生化活性(通过血清碱性磷酸酶评估)、骨量、矿物质密度和生物力学特性。这些结果表明,矿物质供应而非维生素D本身,可能对正常骨矿化以及使PTH增强骨形成很重要。在实验的最后3天进行的平衡研究表明,PTH仅增加了+D组的肠道镁表观吸收。然而,在两个饮食组中,给予PTH后钙和磷的潴留均增加。总之,在血钙和血磷正常的-D大鼠中,PTH治疗降低了内源性激素浓度的升高,并改善了钙和磷的潴留。此外,PTH可能对肠道镁吸收有维生素D依赖性影响。最后,当饮食中提供足够的矿物质时,短期PTH治疗对维生素D缺乏大鼠的骨骼具有合成代谢作用。

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