The influence of the progression of secondary hyperparathyroidism on the set point of the parathyroid hormone-calcium curve.
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.
Bas
S
S
Departamento de Medicina y Cirugía Animal, Universidad de Córdoba, Campus de Rabanales, Ctra Madrid-Cádiz km 396, 14014 Córdoba, Spain.
Aguilera-Tejero
E
E
Bas
A
A
Estepa
J C
JC
Lopez
I
I
Madueño
J A
JA
Rodriguez
M
M
D000818:Animals; D002117:Calcitriol / Q000097:blood; D002118:Calcium / Q000097:blood*; D003404:Creatinine / Q000097:blood; D018450:Disease Progression; D005110:Extracellular Space / Q000378:metabolism; D005260:Female; D006962:Hyperparathyroidism, Secondary / Q000097:blood* / Q000378:metabolism / Q000473:pathology; D008297:Male; D009392:Nephrectomy; D010280:Parathyroid Glands / Q000378:metabolism / Q000473:pathology; D010281:Parathyroid Hormone / Q000097:blood* / Q000235:genetics; D010710:Phosphates / Q000097:blood; D012333:RNA, Messenger / Q000032:analysis; D012372:ROC Curve; D011817:Rabbits; D018167:Receptors, Calcitriol / Q000235:genetics; D044169:Receptors, Calcium-Sensing / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D010281:Parathyroid Hormone; D010710:Phosphates; D012333:RNA, Messenger; D018167:Receptors, Calcitriol; D044169:Receptors, Calcium-Sensing; D003404:Creatinine; D002117:Calcitriol; D002118:Calcium