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Query: UMLS:C0020437 (hypercalcemia)
 10,293 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The mammalian fetus is maintained hypercalcaemic relative to its mother by the action of a calcium pump believed to be located at the basement membranes of the epithelial cells of the fetal chorion. It has recently been demonstrated that the activity of this putative pump is stimulated by a new fetal hormone, parathyroid hormone-related protein, described originally as the product of a human BEN cell line which was derived from a lung tumour associated with hypercalcaemia of malignancy. Whereas the circulating level of immunoreactive parathyroid hormone in the fetus is very low, in keeping with the hypercalcaemia, the plasma concentrations of bioactive parathyroid hormone and parathyroid hormone-related protein can be measured using a sensitive cytochemical bioassay and the separate concentrations assessed by pre-incubation with appropriate antisera. The total plasma concentration of both hormones is inversely related to the prevailing calcium ion concentration but the set point of parathyroid hormone-related protein is probably higher than that for parathyroid hormone. Probably as a result of the hypercalcaemia, the circulating concentration of calcitonin is also higher than in maternal plasma and may serve to limit bone resorption to favour net bone accretion as part of the overall growth of the fetus. Vitamin D and its most active metabolite, 1,25(OH)2D, can pass across the placenta in either direction, in contrast to most peptide hormones. In addition to the supply of some 1,25(OH)2D by the mother to her fetus, the fetal placenta and fetal kidneys can all synthesize 1,25(OH)2D. The relative concentrations circulating in maternal and fetal plasma pools vary with the species, presumably as a result of differing importance of the three sources of supply to the fetus and the relative concentrations of vitamin D-binding protein circulating in mother and fetus. The importance of parathyroid hormone-related protein derived from fetal parathyroid glands has been clearly demonstrated in the fetal sheep. Such animals develop rickets following the removal of their parathyroid glands, despite the demonstration of this substance in fetal placental membranes. However, the relative importance of the parathyroid glands versus the placenta and its membranes as the principal source of parathyroid hormone-related protein remains to be elucidated and may vary with species.
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PMID:Development of endocrine pathways in the regulation of calcium homeostasis. 269 50

It has been suggested that the parathyroid glands and the kidneys are insensitive to the high extracellular calcium levels found in familial benign hypercalcaemia (FBH) (familial hypocalciuric hypercalcaemia) and that there may be a general disorder of the plasma membrane 'calcium pump'. We have found that the activity of the calcium-stimulated, magnesium-dependent ATPase of erythrocyte ghost membranes from patients with FBH was significantly higher (p less than 0.01) than that from normal subjects. Values in FBH, as a group, were higher than those in primary hyperparathyroidism, but the difference was not significant. We suggest that the membrane abnormality in FBH could be a disorder of the regulation of the calcium pump.
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PMID:Calcium-ATPase activity in erythrocyte ghosts from patients with familial benign hypercalcaemia. 316 Jan 2

Parathyroid hormone (PTH)-like bioactivity, assayed as adenylate cyclase response in UMR 106-01 osteogenic sarcoma cells, was present in extracts of sheep fetal and maternal parathyroid glands and placenta. Preincubation of extracts with PTH(1-34) antiserum inhibited approximately 40% of the bioactivity in fetal parathyroid extracts, 50% in maternal parathyroid extracts, but only 10% of the bioactivity in the placental extract. Partial purification of placental extracts by chromatography yielded fractions containing PTH-like bioactivity which were similar in behaviour to that of PTH-related protein (PTHrP) from a human lung cancer cell line (BEN). An antiserum against synthetic PTHrP(1-16) partially inhibited the bioactivity of the placental extract and synthetic PTHrP(1-34), but had no effect on the bioactivity of bovine PTH(1-34) or bovine PTH(1-84). The placental PTH-like bioactivity was higher in mid- than in late gestation. Fetal parathyroid glands contained the highest PTH-like bioactivity. Thyroparathyroidectomy of one fetal twin lamb in each of 16 ewes between 110 and 125 days of gestation resulted in decreases of the plasma calcium concentration and reversal of the placental calcium gradient that existed between the ewe and the intact fetus. Perfusion of the placenta of each twin in anaesthetized ewes was carried out sequentially with autologous fetal blood in the absence of the exsanguinated fetus. The plasma calcium concentration in the blood perfusing the placenta of each twin increased, but reached a plateau at a lower concentration in the perfusing blood of thyroparathyroidectomized fetuses than in that of the intact fetuses. Addition of extracts of fetal parathyroid glands or of partially purified PTHrP resulted in further increases in plasma calcium in the autologous blood perfusing the placentae of thyroparathyroidectomized fetuses, but addition of bovine PTH(1-84) or rat PTH(1-34) had no effect. The presence of this PTH-like protein in the fetal parathyroid gland and placenta may contribute to the relative hypercalcaemia of the fetal lamb. This protein, which is similar to PTHrP associated with humoral hypercalcaemia of malignancy, stimulates the placental calcium pump responsible for maintaining a relative fetal hypercalcaemia during gestation.
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PMID:Evidence for a novel parathyroid hormone-related protein in fetal lamb parathyroid glands and sheep placenta: comparisons with a similar protein implicated in humoral hypercalcaemia of malignancy. 337 58

The fundamental biochemical abnormality in familial benign hypercalcaemia (FBH) (familial hypocalciuric hypercalcaemia) is unknown. It seemed possible that, since the kidneys and the parathyroid glands are insensitive to the high extracellular calcium levels, a general disorder of the regulation of the calcium pump on the plasma membrane is present. We obtained evidence suggesting that active calcium efflux by erythrocytes from patients with FBH (85.7 +/- 4.5 mumol 1(-1) min-1) is higher (P less than 0.005) than that by erythrocytes from control subjects (78.6 +/- 4.1 mumol 1(-1) min-1) or from patients with primary hyperparathyroidism (77.5 +/- 5.2 mumol 1(-1) min-1, P less than 0.05). Calcium influx into erythrocytes was normal in FBH and in primary hyperparathyroidism.
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PMID:Familial benign hypercalcaemia: a possible abnormality in calcium transport by erythrocytes. 609 79

The hypothesis that a global defect in cellular calcium transport may be critical in the development of familial benign hypercalcaemia (FBH) was investigated. Nine hypercalcaemic patients from a kindred with FBH and nine normal subjects were evaluated. Our results indicate that calcium pump activity in the FBH kindred was significantly higher (28%, P < 0.005) when compared to normal subjects. These findings suggest that alterations in calcium pump activity in target tissues may play a role in the development of FBH.
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PMID:Increased erythrocyte calcium pump activity in a kindred with familial benign hypercalcaemia. 765 14