The stimulation of parathyroid hormone (PTH) secretion by hypocalcemia is reduced when hypocalcemia is preceded by hypercalcemia. The present study investigates whether the duration and degree of hypercalcemia influence the reduced PTH response to hypocalcemia after hypercalcemia. In addition, the implication of the arachidonic acid (AA) signaling pathway in this effect is evaluated. The PTH response to hypocalcemia has been studied in a control group and in four groups of rabbits subjected to hypercalcemia for different periods of time (between 30 and 120 min) and at two levels of hypercalcemia (1 x 9 and 2 x 1 mM). AA levels have been measured in parathyroid glands from rabbits subjected to hyper- and hypocalcemia. When compared with controls, rabbits that had been hypercalcemic (2 x 1 mM) for 2 h showed a markedly attenuated PTH response to hypocalcemia (50% of normal PTHmax), rabbits that had been in hypercalcemia (2 x 1 mM) for 75 min had an intermediate PTH response to hypocalcemia (70% of normal PTHmax) and rabbits that had been subjected to either 30 min hypercalcemia of 2 x 1 mM or 120 min hypercalcemia of 1 x 9 mM had a normal PTH response to hypocalcemia. AA levels increased in hypercalcemia and decreased in hypocalcemia; however, no differences were observed at either calcium level in short-time (30 min) versus long-time (120 min) hypercalcemia. In conclusion, the attenuated PTH response to hypocalcemia after hypercalcemia is dependent on both the period of time that the parathyroid glands have been exposed to hypercalcemia and the degree of hypercalcemia. In addition, this reduced PTH response does not seem to be related to changes in the AA signaling pathway.

The influence of secondary hyperparathyroidism (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.