The regulation of parathyroid hormone secretion and synthesis.
The regulation of parathyroid hormone secretion and synthesis.
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DOI：
10.1681/asn.2010020186
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发表时间：
2011-03
期刊：
影响因子：
--
通讯作者：
Thompson JR
中科院分区：
文献类型：
--
作者：
Kumar R;Thompson JR
继发性甲状旁腺功能亢进症通常出现在慢性肾功能衰竭的病程中，有时出现在肾移植后。了解甲状旁腺激素(PTH)合成和分泌的正常调节机制，对于设计调节肾功能不全后甲状旁腺过度活动和增生的方法具有重要意义。甲状旁腺细胞上的G蛋白偶联钙敏感受体介导甲状旁腺激素分泌对血钙变化的快速调节，而甲状旁腺细胞上mRNA结合蛋白编码甲状旁腺素的稳定性的改变则是对血钙长期变化的反应。与肠道钙吸收和血钙变化无关，1-α，25-二羟基维生素D还通过与维生素D受体结合而抑制甲状旁腺素的转录，维生素D受体与维甲酸X受体异构化结合甲状旁腺素基因内的维生素D反应元件。1甲状旁腺素，25-二羟基维生素D额外调节钙敏感受体的表达，间接改变α的分泌。在肾功能衰竭的2°甲状旁腺功能亢进中，钙感受器和维生素D受体浓度降低，甲状旁腺细胞内信使核糖核酸结合蛋白活性改变，甲状旁腺激素分泌增加，此外，更广泛地认识到血清钙、磷和1-α，25-二羟基维生素D的变化。通过纠正血清钙和磷浓度以及给予维生素D类似物和类钙剂来治疗继发性甲状旁腺功能亢进，未来可能会通过改变甲状旁腺激素编码信使核糖核酸的稳定性的药物来加强。
Secondary hyperparathyroidism classically appears during the course of chronic renal failure and sometimes after renal transplantation. Understanding the mechanisms by which parathyroid hormone (PTH) synthesis and secretion are normally regulated is important in devising methods to regulate overactivity and hyperplasia of the parathyroid gland after the onset of renal insufficiency. Rapid regulation of PTH secretion in response to variations in serum calcium is mediated by G-protein coupled, calcium-sensing receptors on parathyroid cells, whereas alterations in the stability of mRNA-encoding PTH by mRNA-binding proteins occur in response to prolonged changes in serum calcium. Independent of changes in intestinal calcium absorption and serum calcium, 1α,25-dihydroxyvitamin D also represses the transcription of PTH by associating with the vitamin D receptor, which heterodimerizes with retinoic acid X receptors to bind vitamin D-response elements within the PTH gene. 1α,25-Dihydroxyvitamin D additionally regulates the expression of calcium-sensing receptors to indirectly alter PTH secretion. In 2°HPT seen in renal failure, reduced concentrations of calcium-sensing and vitamin D receptors, and altered mRNA-binding protein activities within the parathyroid cell, increase PTH secretion in addition to the more widely recognized changes in serum calcium, phosphorus, and 1α,25-dihydroxyvitamin D. The treatment of secondary hyperparathyroidism by correction of serum calcium and phosphorus concentrations and the administration of vitamin D analogs and calcimimetic agents may be augmented in the future by agents that alter the stability of mRNA-encoding PTH.