Heterogeneity of Parathyroid Hormone. CLINICAL AND PHYSIOLOGIC IMPLICATIONS

Silverman, Robert A.; Yalow, Rosalyn S.

doi:10.1172/jci107380

Cited by 211 publications

(88 citation statements)

References 22 publications

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“…PTH regulates plasma calcium concentration and maintains skeletal integrity (8). PTH receptors are present throughout the cardiovascular system, including in smooth muscle cells, endothelial cells and cardiomyocytes (9)(10)(11).…”

Section: Introductionmentioning

confidence: 99%

Parathyroid hormone promotes osteoblastic differentiation of endothelial cells via the extracellular signal‑regulated protein kinase 1/2 and nuclear factor‑κB signaling pathways

Cheng

Ling³

et al. 2017

Exp Ther Med

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Abstract. Vascular calcification (VC) occurs in patients with chronic kidney disease (CKD) and contributes to cardiovascular dysfunction and mortality. Parathyroid hormone (PTH) is a crucial regulator of VC. High PTH serum levels constitute as a major risk factor for patients with CKD. However, the effect and mechanism of PTH on osteoblastic differentiation in endothelial cells have not been fully elucidated. In the present study, the role of PTH in VC was investigated using an in vitro calcification model. Endothelial cells were stimulated with PTH in the femto-to picomolar range. As determined by western blot analysis and ELISA, osteoblastic differentiation, as indicated by the BMP2 marker, occurred with maximum effect at 1x10 -10 mmol/l PTH. The results indicate that PTH promotes osteoblastic differentiation of endothelial cells, as demonstrated by the increased expression of bone morphogenetic protein (BMP) 2 and BMP4. In addition, western blot analysis revealed that PTH activated the extracellular signal-regulated protein kinase (Erk)1/2 and nuclear factor (NF)-κB signaling pathways. However, reverse transcription-quantitative polymerase chain reaction demonstrated that inhibitors specific to Erk1/2 and NF-κB eradicated the effect of PTH treatment on BMP2, BMP4, ALP and RUNX2 expression. These results demonstrate that PTH promotes the osteoblastic differentiation of endothelial cells via the Erk1/2 and NF-κB signaling pathways, which suggests a potential role of PTH in the promotion of VC. These findings provide an insight into the association between PTH and cardiovascular disease.

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Section: Introductionmentioning

confidence: 99%

Parathyroid hormone promotes osteoblastic differentiation of endothelial cells via the extracellular signal‑regulated protein kinase 1/2 and nuclear factor‑κB signaling pathways

Cheng

Ling³

et al. 2017

Exp Ther Med

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“…4). The 7'000 mol wt COOH-terminal fragment described in the literature (15,17,30,31) as an important circulating form was hardly visualized, unless the shoulder trailing from the intact PTH peak represented part of it. In this instance, the CPD donor blood had undetectable PTH.…”

Section: Methodsmentioning

confidence: 92%

Parathyroid Hormone Response in Newborn Infants during Exchange Transfusion with Blood supplemented with Citrate and Phosphate: Effect of iv Calcium(37)

et al. 1979

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SummaryWe studied secretory parathyroid function in 16 newborn infants, aged 34-137 hr, before, during, and after exchange transfusion with a radioimmunoassay recognizing mainly intact human parathyroid hormone-(1-84) ). Before the exchange transfusion, serum calcium was normal or decreased, whereas parathyroid hormone (PTH) was within or above the range of normal adults. Serum P T H approached a maximum at decreased serum ionized and total calcium levels which were close to the normal range. During the early period of the exchange transfusion, serum ionized calcium was decreased as a result of the administration of considerable amounts of phosphate and citrate i n the donor-blood and P T H was raised to levels seen in hypocalcemic infants before the exchange transfusion. Thereafter, serum ionized calcium remained low, whereas mean PTH concentrations were below basal levels. These inappropriately low P T H levels in relation to lowered serum-ionized calcium concentrations are probably the result of inadequate P T H secretion, which is enhanced by withdrawal of large-amounts of presumably biologically active PTH-(1-84) during the exchange transfusion. Serum total calcium.. .on the other hang, was rais& during the exchange transfusion probably as a result of calcium mobilization, and the net calcium balance expressed as the difference of calcium administered and in the withdrawn blood was negative. Even though serum ionized calcium decreased to levels below 2.5 mg/dl during the exchange transfusion, tetany was never observed, iv injections of calcium during the exchange transfusion caused temporary increases in total, but not i n ionized calcium levels and shortening of Q-oTc intervals lasting for less than 1 min. We, therefore, advocate that iv calcium injections at regular time intervals during the exchange transfusion with donor blood preserved in citrate and phosphate should no longer be recommended as a prophylactic measure for preventing the decrease in serum-ionized calcium. SpeculationParathyroid secretory function is inversely related to serum calcium concentrations i n newborn infants. Serum PTH secretion is maximal at serum-ionized and total calcium concentrations close to the normal range despite further reduction to more markedly hypocalcemic levels. ran sit or^ hypoparathyroidism occurs during exchange transfusion as a result of the removal of considerable amounis of biologically active PTH-(1-84).Evidence obtained by David and Anast (10) indicates that serum PTH is low or undetectable during the first 48 hr of life, whereas after 48 hr, there are parallel increases in PTH as well as in total and ionized calcium levels. In newborn infants, exchange transfusion with donor blood preserved in citrate, or citrate and phosphate are used to relieve hyperbilirubinemia (12,21,35,36). This results in a decrease in ionized (1 1, 27, 33) and in a slight increase in total calcium concentrations (1 1, 27). The available evidence indicates that a fall in ionized rather than in total calcium is responsible for a s...

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“…The bone-specific alkaline phosphatase (obtained at age 13) was 86 U/L, a value within the reference interval [30 - and was deemed a candidate for parathyroidectomy (18,19 ). The baseline intact PTH (Immulite 2000) value obtained 1 week before surgery was 10.92 pmol/L (1.27-6.90 pmol/L) and the calcium value was 3.08 mmol/L.…”

Section: Case Historymentioning

confidence: 99%

Persistent Hypercalcemia After Parathyroidectomy in an Adolescent and Effect of Treatment With Cinacalcet HCl

Henrich¹,

Rogol

D'Amour

et al. 2006

Clinical Chemistry

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Background: Hyperparathyroidism is uncommon in adolescence and is more likely to persist after parathyroidectomy than in adults. Cinacalcet HCl is a new calcimimetic that has been used successfully for the treatment of primary and secondary hyperparathyroidism in adults, but its use in adolescents has not been reported. Case: A 16 year-old male presented with hypercalcemia that had persisted for 1.5 years after parathyroidectomy for primary hyperparathyroidism. Parathyroid hormone (PTH) concentrations were nonsupressed despite a mean (SD) serum calcium concentration of 2.82 (0.06) mmol/L. Treatment with cinacalcet HCl was initiated and a pharmacodynamic profile was obtained for serum calcium, phosphorus, and PTH. Cinacalcet HCl normalized serum calcium. The changes in PTH were assay dependent. Issues: We use this case conference to review the evaluation of hypercalcemia in adolescents, examine the changes in relevant laboratory results during treatment with cinacalcet HCl, and discuss differences among assays for PTH. Conclusions: Interpretation of PTH results in patients treated with cinacalcet HCl requires consideration of the pharmacodynamic effects of the drug and the nature of the PTH assay.

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Heterogeneity of Parathyroid Hormone. CLINICAL AND PHYSIOLOGIC IMPLICATIONS

Cited by 211 publications

References 22 publications

Parathyroid hormone promotes osteoblastic differentiation of endothelial cells via the extracellular signal‑regulated protein kinase 1/2 and nuclear factor‑κB signaling pathways

Parathyroid hormone promotes osteoblastic differentiation of endothelial cells via the extracellular signal‑regulated protein kinase 1/2 and nuclear factor‑κB signaling pathways

Parathyroid Hormone Response in Newborn Infants during Exchange Transfusion with Blood supplemented with Citrate and Phosphate: Effect of iv Calcium(37)

Persistent Hypercalcemia After Parathyroidectomy in an Adolescent and Effect of Treatment With Cinacalcet HCl

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