Goodman William G, Quarles L D
Division of Nephrology, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
Kidney Int. 2008 Aug;74(3):276-88. doi: 10.1038/sj.ki.5002287. Epub 2007 Jun 13.
The identification of the calcium-sensing receptor (CaSR) and the clarification of its role as the major regulator of parathyroid gland function have important implications for understanding the pathogenesis and evolution of secondary hyperthyroidism in chronic kidney disease (CKD). Signaling through the CaSR has direct effects on three discrete components of parathyroid gland function, which include parathyroid hormone (PTH) secretion, PTH synthesis, and parathyroid gland hyperplasia. Disturbances in calcium and vitamin D metabolism that arise owing to CKD diminish the level of activation of the CaSR, leading to increases in PTH secretion, PTH synthesis, and parathyroid gland hyperplasia. Each represents a physiological adaptive response by the parathyroid glands to maintain plasma calcium homeostasis. Studies of genetically modified mice indicate that signal transduction via the CaSR is a key determinant of parathyroid cell proliferation and parathyroid gland hyperplasia. Because enlargement of the parathyroid glands has important implications for disease progression and disease severity, it is possible that clinical management strategies that maintain adequate calcium-dependent signaling through the CaSR will ultimately prove useful in diminishing parathyroid gland hyperplasia and in modifying disease progression.
钙敏感受体(CaSR)的鉴定及其作为甲状旁腺功能主要调节因子作用的阐明,对于理解慢性肾脏病(CKD)继发性甲状腺功能亢进的发病机制和演变具有重要意义。通过CaSR的信号传导对甲状旁腺功能的三个不同组成部分有直接影响,包括甲状旁腺激素(PTH)分泌、PTH合成和甲状旁腺增生。由于CKD引起的钙和维生素D代谢紊乱会降低CaSR的激活水平,导致PTH分泌增加、PTH合成增加和甲状旁腺增生。每一种都代表甲状旁腺为维持血浆钙稳态而做出的生理适应性反应。对基因改造小鼠的研究表明,通过CaSR的信号转导是甲状旁腺细胞增殖和甲状旁腺增生的关键决定因素。由于甲状旁腺肿大对疾病进展和疾病严重程度具有重要影响,通过CaSR维持足够的钙依赖性信号传导的临床管理策略最终可能被证明有助于减少甲状旁腺增生和改变疾病进展。