The calcemic response to PTH in the rat: Effect of elevated PTH levels and uremia

Bover, Jordi; Jara, Aquiles; Trinidad, Pedro; Rodriguez, Mariano; Martín‐Malo, Alejandro; Felsenfeld, Arnold J.

doi:10.1038/ki.1994.276

Cited by 45 publications

(25 citation statements)

References 24 publications

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“…In patients and animals with kidney failure, secondary hyperparathyroidism develops and serum PTH levels may exceed 100 pM (Bover et al 1994, de Francisco 2004. Transgenic mice with parathyroid-targeted overexpression of cyclin D1 exhibit mild hyperparathyroidism, with PTH ranging between 13 and 16 pM -3-4-fold higher than their age-matched wild-type littermates (2-4 pM) -and a 20-30% increase in total serum calcium (Imanishi et a.…”

Section: Discussionmentioning

confidence: 99%

Short-term continuous infusion of human parathyroid hormone 1–34 fragment is catabolic with decreased trabecular connectivity density accompanied by hypercalcemia in C57BL/J6 mice

Iida-Klein

Lu²,

Kapadia³

et al. 2005

Journal of Endocrinology

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Parathyroid hormone (PTH) stimulates bone resorption as well as bone formation in vivo and in organ culture. The catabolic actions of PTH have been recognized in patients with hyperparathyroidism, or with acute infusion of the N-terminal 1-34 fragment of human PTH (hPTH1-34). Whereas the anabolic actions of daily injection with PTH have been well studied in both humans and mice, the catabolic actions of PTH on murine bone remain to be defined. To do this we sought to create a model with short-term, sustained hyperparathyroidism using osmotic infusion pumps. We treated 10-week-old female C57BL/J6 mice with continuous infusion of hPTH1-34 (8·1 pmol/0·25 µl per h, equivalent to 40 µg/kg per day) or vehicle for 2 weeks, using Alzet osmotic pumps. Bone mineral density (BMD), serum total calcium, hPTH1-34, mouse intact PTH (mPTH1-84), osteocalcin and mouse tartrate-resistant acid phosphatase (mTRAP) activity, and microarchitectural variables of the distal femur were measured. Separately, we compared the effects of intermittent daily injection of hPTH1-34 (40 µg/kg per day) with continuous infusion of hPTH1-34 on BMD and bone markers. Exogenous hPTH1-34 was detected only in the PTH-infused mice. Both intermittent and continuous treatment with hPTH1-34 markedly suppressed endogenous mPTH1-84, but only the latter induced hypercalcemia. Daily PTH injection significantly increased both serum osteocalcin and mTRAP, while continuous PTH infusion showed a strong trend to stimulate mTRAP, with a slight but non-significant increase in osteocalcin. There were significant differences in BMD at all sites between animals treated with the same daily dose of intermittent and continuous hPTH1-34. Microcomputed tomography (µCT) analysis of the distal femurs revealed that hPTH1-34 infusion significantly decreased trabecular connectivity density (P<0·05). Thus, the murine bone response to continuous PTH infusion was quite different from that seen with daily PTH injection. Short-term infusion of hPTH1-34 appears to be a good model to study the mechanisms underlying the catabolic action of PTH in mice.

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Section: Discussionmentioning

confidence: 99%

Short-term continuous infusion of human parathyroid hormone 1–34 fragment is catabolic with decreased trabecular connectivity density accompanied by hypercalcemia in C57BL/J6 mice

Iida-Klein

Lu²,

Kapadia³

et al. 2005

Journal of Endocrinology

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“…Studies in normal and azotemic rats have shown that high dietary phosphate greatly increases PTH values (15,40). Conversely, dietary phosphate restriction reduces PTH values in normal rats and minimizes increases in PTH values in azotemic rats (13,41). Even in normal rats and humans who are given a single meal that contains a high phosphate content, it has been shown that postprandial PTH values increase (42)(43)(44).…”

Section: Basal 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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“…Massry et al [15] demonstrated a reduced calcemic response to infusion of parathyroid extract to 105 subjects with varying degrees of renal failure. A diminished calcemic response to PTH in chronic kidney disease has also been demonstrated in animal studies [16][17][18][19][20][21][22][23][24], and using dogs with chronic kidney disease, Galceran et al [24] found that the calcemic response to PTH was restored following parathyroidectomy. Furthermore, a blunted cAMP response to PTH extract was observed by Olgaard et al [25] in isolated perfused bones obtained from uremic dogs.…”

Section: Discussionmentioning

confidence: 88%

Regulation of PTH1 receptor expression by uremic ultrafiltrate in UMR 106–01 osteoblast-like cells

Disthabanchong

Hassan

McConkey

et al. 2004

Kidney International

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The calcemic response to PTH in the rat: Effect of elevated PTH levels and uremia

Cited by 45 publications

References 24 publications

Short-term continuous infusion of human parathyroid hormone 1–34 fragment is catabolic with decreased trabecular connectivity density accompanied by hypercalcemia in C57BL/J6 mice

Short-term continuous infusion of human parathyroid hormone 1–34 fragment is catabolic with decreased trabecular connectivity density accompanied by hypercalcemia in C57BL/J6 mice

Dynamics of Parathyroid Hormone Secretion in Health and Secondary Hyperparathyroidism

Regulation of PTH1 receptor expression by uremic ultrafiltrate in UMR 106–01 osteoblast-like cells

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