Early response of the parathyroid gland to withdrawal of a calcimimetic coniDound in uremic rats

摘要

Continuous stimulation of the parathyroid glands by a combination of serum phosphorus elevation, Ca2+ reduction, and markedly reduced serum calcitriol leads to increased parathyroid hormone (PTH) synthesis and secretion as well as parathyroid hyperplasia, both of which are characteristics of secondary hyperparathyroidism (SHPT) (8, 10, 26, 42, 43). During the development of parathyroid hyperplasia, down-regulation of Ca2+-sensing receptor (CaSR) and vitamin D receptor (VDR) expression renders parathyroid cells unable to respond appropriately to changes in serum Ca2+ and calcitriol levels. Studies in normal rats and a rat model of renal failure have demonstrated that parathyroid cell proliferation is associated with a decrease in CaSR and VDR expression (4, 25, 29). Both VDR activators (VDRAs) and calcimimetics can suppress parathyroid cell hyperactivity by mediating the expression of these receptors. An increase in the parathyroid concentration of calcitriol upregulates parathyroid VDR expression in animals (14), and activation of CaSR by calcimimetics induces both parathyroid CaSR (29) and VDR expression (27) in uremic rats.