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Predominant role of 250HD in the negative regulation of PTH expression: Clinical relevance for hypovitaminosis D

机译:250HD在PTH表达负调控中的主要作用:维生素D缺乏的临床意义

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Although severe deficiency of bioactive vitamin D (1,2501-121)) causes rickets, mild insufficiency of the hormone, known as hypovitammosis D, is responsible for the occurrence of secondary hyperparathyroidism and osteoporosis. To clarify the pathophysiology of the disease, we studied the negative feedback effect of 1,25OH2D and its precursor 25OHD on the transcriptional activity of parathyroid hormone (PTH) gene using the PT-r parathyroid cell line. We found that PT-r cells express endogenous I (x-hydroxylase as well as PTH mRNAs. We also found the potent suppressive effect of physiological concentration of 25OHD on the transcriptional activity of PTH gene. A similar effect was obtained with 1,250H2D but only with pharmacological concentration. Interestingly, the effect of 25OHD was completely abolished when the cells were treated with 1 alpha-hydroxylase inhibitor ketoconazole. These results suggest that the negative feedback regulation of vitamin D on PTH gene transcription occurs not by the end-product 1,250H2D but by its prohormone 25OHD via intracellular activation by 1 alpha-hydroxylase within the parathyroid cells. (c) 2008 Elsevier Inc. All rights reserved.
机译:尽管严重缺乏生物活性维生素D(1,2501-121)会导致病,但激素的轻度不足(称为维生素缺乏症D)可导致继发性甲状旁腺功能亢进症和骨质疏松症的发生。为了阐明该疾病的病理生理,我们使用PT-r甲状旁腺细胞系研究了1,25OH2D及其前体25OHD对甲状旁腺激素(PTH)基因转录活性的负反馈作用。我们发现PT-r细胞表达内源性I(x-羟化酶以及PTH mRNA)。我们还发现生理浓度的25OHD对PTH基因的转录活性具有有效的抑制作用。1,250H2D可获得类似的效果,但仅有趣的是,用1种α-羟化酶抑制剂酮康唑处理细胞后,完全消除了25OHD的作用,这些结果表明维生素D对PTH基因转录的负反馈调节不是最终产物1,250H2D引起的。但通过甲状旁腺细胞内的1α-羟化酶通过细胞内激活作用通过其前激素25OHD(c)2008 Elsevier Inc.保留所有权利。

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