Objective: To investigate the influence of acute and chronic hypercalcemia on the parathyroid hormone (PTH) response to hypocalcemia. Design: The PTH response to hypocalcemia has been evaluated in three groups of rabbits: Group I, normal rabbits, Group II, normal rabbits subjected to an acute hypercalcemic clamp (induced by CaCl 2 infusion) and Group III, rabbits with chronic hypercalcemia (due to surgical reduction of renal mass). Results: In Group I (baseline Ca 2þ ¼ 1:69^0:02 mM), hypocalcemia resulted in stimulation of PTH secretion which reached a maximum (PTHmax) of 91:7^6:4 pg=ml: In rabbits from Group II, which also had normal baseline Ca 2+ ð1:70^0:02 mMÞ; plasma Ca 2+ was maintained at an elevated level for 2 h, at around 2.05 mM. The PTH response to hypocalcemia in Group II was attenuated and the PTHmax in these rabbits was 45:6^7:4 pg=ml: In rabbits from Group III, baseline Ca 2+ was elevated ð2:06^0:06 mMÞ for 1 month. The PTH response to hypocalcemia in Group III was esentially the same as in Group I and PTHmax reached levels of 94:8^9:9 pg=ml: Conclusions: A difference in PTH response to hypocalcemia has been found in rabbits after exposure to either acute or chronic hypercalcemia. After acute hypercalcemia, an attenuated PTH response to hypocalcemia has been identified. Chronic hypercalcemia, however, did not influence the PTH response to hypocalcemia.

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The influence of secondary hyperparathyroidism (2 HPT) on the set point of the parathyroid hormone (PTH)-Ca 2+ 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-Ca 2+ curve. The PTH-Ca 2+ 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-Ca 2+ 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-Ca 2+ curve in response to decreased extracellular Ca 2+ 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 Ca 2+ 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.