The influence of the progression of secondary hyperparathyroidism on the set point of the parathyroid hormone-calcium curve

The influence of secondary hyperparathyroidisrn (2 HPT) on the set point of the parathyroid hormone (PTH)-Ca2+ curve is controversial. In vitro experiments have shown an increase in the set point. However, clinical studies with hemodialysis patients have provided a variety of results (increases, decreases and no changes in the set point have been reported). The present study was designed to investigate the influence of the progression of 2 HPT on the set point of the PTH-Ca2+ curve. The PTH-Ca2+ curve and the expression of parathyroid calcium receptor (CaR mRNA) and vitamin D receptor (VDR mRNA) have been studied in normal rabbits (group I, n=9) and in nephrectomized rabbits (group II, n=18) at two stages after inducing 2 HPT: 2-3 weeks (group IIA) and 5-6 weeks (group IIB). In group I, the set point of the PTH-Ca2+ curve was 1.63 +/- 0.03 mM. A progressive hypocalcemia was detected during the evolution of 2 HPT (groups IIA and IIB). Rabbits from group IIA had a significant (P<0.001) decrease in the set point to values of 1.45 +/- 0.02 mM. However, the set point increased significantly in group IIB (P<0.001) to 1.56 +/- 0.03 mM. CaR mRNA was similarly decreased in groups IIA (39 +/- 12%) and IIB (48 +/- 7%). No changes were detected in VDR mRNA. In conclusion, a reduction in the set point of the PTH-Ca2+ curve in response to decreased extracellular Ca2+ was detected in the early phases of 2 HPT. However, with the progression of 2 HPT the set point tended to increase even though extracellular Ca2+ was markedly decreased. The increase in the set point in the course of 2 HPT seems to be a complex process that cannot be fully explained by changes in parathyroid CaR mRNA or VDR mRNA.