Defective regulation of the cytosolic Ca2+ activity in parathyroid cells from patients with hyperparathyroidism

1984 ◽  
Vol 4 (11) ◽  
pp. 909-915 ◽  
Author(s):  
Rolf Larsson ◽  
Chris Wallfelt ◽  
Håkan Abrahamsson ◽  
Erik Gylfe ◽  
Sverker Ljunghall ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Calcium Concentration ◽  
Close Correlation ◽  
Extracellular Calcium ◽  
Hormone Release ◽  
Extracellular Calcium Concentration ◽  
The Individual ◽  
Release Characteristic ◽  
In Cells

The parathyroid hormone (PTH) release and cytosolic Ca2+ activity were determined in normal bovine parathyroid cells and parathyroid cells obtained from patients with hyperparathyroidism (HPT). There was a sigmoid relation between the cytosolic Ca2+ activity and the extracellular calcium concentration between 0.5 and 6.0 mmol/l. The PTH release was inhibited in parallel with the rise in the cytosolic Ca2+ activity. Both the hormone release and the cytosolic Ca2+ activity were lower in cells from human adenomas and hyperplastic glands∼ and in comparison with the bovine preparations these ceils had higher set points for the cytosolic Ca2+ activity and PTH release. There was a close correlation between the individual set points for the cytosolic Ca2+ activity and PTH release in a material containing both normal and pathological cells. The results indicate that the abnormal PTH release characteristic of HPT is due to a defective regulation of the cytosolic Ca2+ activity.

Relationship between external and cytoplasmic calcium concentrations, parathyroid hormone release and weight of parathyroid glands in human hyperparathyroidism

1988 ◽  
Vol 116 (3) ◽  
pp. 457-464 ◽  
Author(s):  
C. Wallfelt ◽  
E. Gylfe ◽  
R. Larsson ◽  
S. Ljunghall ◽  
J. Rastad ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Calcium Concentration ◽  
Hormone Release ◽  
Cytoplasmic Calcium ◽  
Serum Concentrations ◽  
Maximal Inhibition ◽  
Adult Cattle ◽  
Calcium Effects ◽  
The Individual ◽  
Parathyroid Hormone Release

ABSTRACT Parathyroid hormone (PTH) release and cytoplasmic calcium concentrations were investigated at ambient calcium concentrations of 0·5–3·0 mmol/l in dispersed parathyroid cells from 44 hypercalcaemic patients with primary or uraemic hyperparathyroidism (HPT). In comparison with parathyroid cells from adult cattle, release of PTH by human preparations was reduced and values of the ambient calcium concentration causing half-maximal inhibition of PTH release (median effective dose, ED50) were significantly increased. Half-maximal inhibition of PTH release was obtained with concentrations of cytoplasmic calcium almost identical to the concentrations of ionized calcium in the plasma of the individual patients. Cytoplasmic concentrations of calcium in the parathyroid cells were inversely related to release of PTH. Concentrations of cytoplasmic calcium were significantly lower in human than in bovine cells and the ED50 for ambient calcium increase on cytoplasmic calcium was raised to the same extent as the ED50 for ambient calcium inhibition of PTH release in human compared with bovine cells. The magnitude of the increased ED50 for ambient calcium inhibition of PTH release and increase of cytoplasmic calcium concentration was similar in adenomas and sporadic as well as hereditary primary hyperplasias, but the secretion was the least aberrant in uraemic hyperplasias, although they had by far the largest glandular mass. Serum concentrations of total calcium before surgery correlated with the ED50 for ambient calcium effects of PTH release and cytoplasmic calcium, but not with glandular weight. These findings demonstrate a universally abnormal regulation of cytoplasmic calcium in HPT and its importance for PTH release, and that disturbance of cytoplasmic calcium rather than the increased glandular mass contributes to the hypercalcaemia in adenomatous and hyperplastic HPT. J. Endocr. (1988) 116, 457–464

scholarly journals Rare diseases caused by abnormal calcium sensing and signalling

Endocrine ◽  
2021 ◽  
Vol 71 (3) ◽  
pp. 611-617
Author(s):  
Judit Tőke ◽  
Gábor Czirják ◽  
Péter Enyedi ◽  
Miklós Tóth
Keyword(s):  
Calcium Homeostasis ◽  
Calcium Concentration ◽  
Gene Mutations ◽  
Cell Types ◽  
Bartter Syndrome ◽  
Extracellular Calcium ◽  
Calcium Signal ◽  
Extracellular Calcium Concentration ◽  
Calcium Sensing ◽  
Increased Risk

AbstractThe calcium-sensing receptor (CaSR) provides the major mechanism for the detection of extracellular calcium concentration in several cell types, via the induction of G-protein-coupled signalling. Accordingly, CaSR plays a pivotal role in calcium homeostasis, and the CaSR gene defects are related to diseases characterized by serum calcium level changes. Activating mutations of the CaSR gene cause enhanced sensitivity to extracellular calcium concentration resulting in autosomal dominant hypocalcemia or Bartter-syndrome type V. Inactivating CaSR gene mutations lead to resistance to extracellular calcium. In these cases, familial hypocalciuric hypercalcaemia (FHH1) or neonatal severe hyperparathyroidism (NSHPT) can develop. FHH2 and FHH3 are associated with mutations of genes of partner proteins of calcium signal transduction. The common polymorphisms of the CaSR gene have been reported not to affect the calcium homeostasis itself; however, they may be associated with the increased risk of malignancies.

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