PTH(1–84)/PTH(7–84): a balance of power

Friedman, Peter A.; Goodman, William G.

doi:10.1152/ajprenal.00336.2005

Cited by 54 publications

(39 citation statements)

References 83 publications

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“…PTH (7-84) is reputed to be able to antagonize the calcemic response to PTH (1-84) using in vivo experimental protocols. Studies in vitro have shown that PTH (7-84) can induce reduction in bone resorption, which has previously been stimulated by different agonists (38,39). Thus, C-terminal PTH fragments in high concentrations may modulate the actions of PTH on the skeleton.…”

Section: Evolution Of Pth Assaysmentioning

confidence: 98%

PTH—A Particularly Tricky Hormone

Garrett

Sardiwal

Lamb

et al. 2013

Clinical Journal of the American Society of Nephrology

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SummaryPlasma parathyroid hormone (PTH) concentrations are commonly measured in the context of CKD, as PTH concentration elevation is typical in this clinical context. Much has been inferred from this raised PTH concentration tendency, both about the state of skeletal integrity and health and also about the potential clinical outcomes for patients. However, we feel that reliance on PTH concentrations alone is a dangerous substitute for the search for, and use of, more precise and reliable biomarkers. In this article, we rehearse these arguments, bringing together patient-level and analytical considerations for the first time.

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Section: Evolution Of Pth Assaysmentioning

confidence: 98%

PTH—A Particularly Tricky Hormone

Garrett

Sardiwal

Lamb

et al. 2013

Clinical Journal of the American Society of Nephrology

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“…Reasons for the decreased calcemic response to PTH above a serum calcium of 10 mg/dl include (1) the greater gradient of calcium against which PTH must function; (2) the decrease in serum phosphorus is maximal at PTH values two to three times normal and does not decrease much more at higher PTH values (2); (3) the deterioration in renal function resulting from hypercalcemia decreases phosphorus excretion, which, in turn, increases the serum phosphorus concentration, thereby compromising the calcemic action of PTH (2-4); and (4) the proportional increase in the percentage of carboxy-terminal and large truncated amino-terminal PTH fragments of which 7-84 PTH is the prototype (5,6). These PTH fragments seem to antagonize the calcemic action of PTH by binding to the carboxy-terminal PTH (C-PTH) receptor (7)(8)(9) and possibly by inducing internalization of the PTH1 receptor (10).…”

Section: Bifunctional Relationship Between Pth and Serum Calciummentioning

confidence: 99%

“…In normal humans, the non-1-84 PTH fragment represented approximately 20% of the total iPTH measured with the iPTH assay, but in renal failure, the non-1-84 PTH fragment accounted for approximately 50% of the measured PTH (22,23). In the late 1990s, a second-generation iPTH assay was developed in which the amino-terminal antibody was directed against the first six amino acids, in contrast to the first-generation iPTH assay in which the binding sites for the amino terminal have ranged from epitopes 12 to 34 (6,10). Thus, the second-generation assay eliminated the detection of the large, truncated amino-terminal fragments that were being measured with the first-generation iPTH assay (7,24); however, more recent studies showed that the second-generation iPTH assay also detects an N-form of PTH, different from Figure 1.…”

Section: Measurement Of Pthmentioning

confidence: 99%

Dynamics of Parathyroid Hormone Secretion in Health and Secondary Hyperparathyroidism

Felsenfeld

Rodríguez

Aguilera–Tejero

2007

Clinical Journal of the American Society of Nephrology

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This review examines the dynamics of parathyroid hormone secretion in health and in various causes of secondary hyperparathyroidism. Although most studies of parathyroid hormone and calcium have focused on the modification of parathyroid hormone secretion by serum calcium, the relationship between parathyroid hormone and serum calcium is bifunctional because parathyroid hormone also modifies serum calcium. In normal animals and humans, factors such as phosphorus and vitamin D modify the basal parathyroid hormone level and the maximal parathyroid hormone response to hypocalcemia. Certain medications, such as lithium and estrogen, in normal individuals and sustained changes in the serum calcium concentration in hemodialysis patients change the set point of calcium, which reflects the serum calcium concentration at which parathyroid hormone secretion responds. Hypocalcemia increases the basal/maximal parathyroid hormone ratio, a measure of the relative degree of parathyroid hormone stimulation. The phenomenon of hysteresis, defined as a different parathyroid hormone value for the same serum calcium concentration during the induction of and recovery from hypo-and hypercalcemia, is discussed because it provides important insights into factors that affect parathyroid hormone secretion. In three causes of secondary hyperparathyroidism-chronic kidney disease, vitamin D deficiency, and aging-factors that affect the dynamics of parathyroid hormone secretion are evaluated in detail. During recovery from vitamin D deficiency, the maximal parathyroid hormone remains elevated while the basal parathyroid hormone value rapidly becomes normal because of a shift in the set point of calcium. Much remains to be learned about the dynamics of parathyroid hormone secretion in health and secondary hyperparathyroidism. T his review examines the dynamics of parathyroid hormone (PTH) secretion in health and in various causes of secondary hyperparathyroidism with an emphasis on chronic kidney disease (CKD). For better understanding of factors that affect PTH secretion, the PTH-calcium relationship is evaluated with respect to (1) PTH secretion in the baseline state (basal PTH) and its sensitivity to the serum calcium concentration; (2) the maximal PTH response to hypocalcemia and factors that have been reported to modify the maximal PTH response to hypocalcemia; (3) shifts in the set point of calcium for PTH secretion in normal individuals as a result of treatment with medications such as lithium and estrogen and in hemodialysis patients during sustained changes in the serum calcium concentration; (4) the dynamics of PTH secretion in the secondary hyperparathyroidism of CKD, vitamin D deficiency, and aging; and (5) the phenomenon of hysteresis, defined as a different PTH value for the same serum calcium concentration during the induction of and recovery from both hypo-and hypercalcemia. A focus on hysteresis is justified because it provides important insights into how PTH secretion is modified by rate and directional changes in the serum c...

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“…Large N-terminally truncated PTH fragments such as PTH are also normally present in peripheral blood (6). However, PTH (7-84) is suggested to inhibit PTH signaling and to initiate adverse biological effects (6,7).…”

Section: Introductionmentioning

confidence: 99%

Parathyroid hormone (PTH) peptides through the regulation of hyaluronan metabolism affect osteosarcoma cell migration

et al. 2010

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SummaryParathyroid hormone (PTH) strongly stimulates hyaluronan (HA) synthesis and secretion of both normal and carcinogenic cells of the osteoblastic lineage and improves skeletal microarchitecture. HA, a glycosaminoglycan component of the extracellular matrix (ECM), is capable of transmitting ECM-derived signals to regulate cellular function. In this study, we investigated whether the changes of HA metabolism induced by PTH (1-34) and PTH (7-84) peptides in moderately MG-63 and well-differentiated Saos 2 osteosarcoma cell lines, are correlated to their migration capabilities. Our results demonstrate that intermittent PTH (1-34) treatment significantly (P 0.01) supported the migration of MG-63 cells, increased their HA-synthase-2 (HAS2) expression (P 0.001), and enhanced their high-molecular size HA deposition in the pericellular matrix. Both increased endogenous HA production (P 0.01) and treatment with exogenous high-molecular weight HA (P 0.05) correlated to a significant increase of MG-63 cell migration capacity. Transfection with siHAS2 showed that PTH (1-34), mainly through HAS2, enhanced HA and regulated MG-63 cell motility. Interestingly, continuous PTH (1-34) treatment stimulated both Saos 2 cell HAS2 (P 0.001) and HAS1 (P 0.001) isoform expression inhibited their HYAL2 expression (P 0.001) and modestly (P 0.05) enhanced their migration. Therefore, the PTH (1-34) administration mode appears to distinctly modulate the migratory responses of the MG-63 moderately and Saos 2 well-differentiated osteosarcoma cell lines. Conclusively, the obtained data suggest that there is a regulatory effect of PTH (1-34), in an administration mode-dependent manner, on HA metabolism that is essential for osteosarcoma cell migration.

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PTH(1–84)/PTH(7–84): a balance of power

Cited by 54 publications

References 83 publications

PTH—A Particularly Tricky Hormone

PTH—A Particularly Tricky Hormone

Dynamics of Parathyroid Hormone Secretion in Health and Secondary Hyperparathyroidism

Parathyroid hormone (PTH) peptides through the regulation of hyaluronan metabolism affect osteosarcoma cell migration

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