Minerva Center for Calcium and Bone Metabolism, Nephrology Services, Hadassah Hebrew University Medical Center, POB 12000, Jerusalem 91120, Israel.
Endocrinology. 2010 Apr;151(4):1398-402. doi: 10.1210/en.2009-1160. Epub 2009 Dec 23.
PTH regulates serum calcium and phosphate levels and bone strength. The parathyroid is unique in that the trigger for PTH secretion is a low extracellular calcium rather than high calcium as for other hormones. The parathyroid senses small changes in serum calcium through the seven-trans-membrane G protein-coupled calcium receptor to alter PTH secretion. PTH then acts on bone and kidney to correct serum calcium. Parathyroid cells have few secretory granules as compared with other endocrine cells, and therefore PTH production is regulated largely at the levels of PTH gene expression and parathyroid cell proliferation. The regulation of PTH gene expression by changes in calcium and phosphate and in chronic kidney failure is posttranscriptional involving the binding of trans-acting proteins to a defined cis element in the PTH mRNA 3'-untranslated region. These protein-PTH mRNA interactions are orchestrated by the peptidyl-prolyl isomerase Pin1. This review discusses the mechanisms of regulation of PTH mRNA stability determining serum PTH levels and mineral metabolism.
甲状旁腺激素调节血清钙和磷水平以及骨骼强度。甲状旁腺的独特之处在于，甲状旁腺激素分泌的触发因素是细胞外钙浓度降低，而不是像其他激素那样是钙浓度升高。甲状旁腺通过七跨膜 G 蛋白偶联钙受体感知血清钙的微小变化，从而改变甲状旁腺激素的分泌。甲状旁腺激素随后作用于骨骼和肾脏以纠正血清钙。与其他内分泌细胞相比，甲状旁腺细胞的分泌颗粒较少，因此甲状旁腺激素的产生主要在甲状旁腺激素基因表达和甲状旁腺细胞增殖的水平上受到调节。钙和磷的变化以及慢性肾衰竭对甲状旁腺激素基因表达的调节是转录后调节，涉及反式作用蛋白与甲状旁腺激素 mRNA 3'非翻译区中特定顺式元件的结合。这些蛋白-PTH mRNA 相互作用是由肽基脯氨酰顺反异构酶 Pin1 协调的。这篇综述讨论了决定血清 PTH 水平和矿物质代谢的 PTH mRNA 稳定性调节机制。
