Parathyroid Hormone

and, Robert A. Nissenson; Jüppner, Harald

doi:10.1002/9781118453926.ch26

Cited by 18 publications

(12 citation statements)

References 54 publications

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“…The other outstanding features of advanced CKD are low 1,25(OH) 2 D levels, secondary hyperparathyroidism, and hypocalcaemia. FGF23 suppresses the production of 1,25(OH) 2 D from the kidney due to decreased 1α hydroxylation of 25-hydroxy vitamin D. The resulting low concentrations of 1,25(OH) 2 D lessen the suppression of the parathyroid glands by this active form of vitamin D5, leading to the enhanced secretion of PTH, and also the induction of hypocalcaemia by decreasing calcium absorption from the colon19. The high levels of circulating phosphate in late-stage CKD decrease the concentration of ionised calcium.…”

Section: Discussionmentioning

confidence: 99%

“…These main mechanisms of parathyroid regulation in CKD by FGF23, vitamin D, calcium, and phosphate have been confirmed in many studies to date. Thus, secondary hyperparathyroidism has been postulated to be the direct result of low 1,25(OH) 2 D levels and hypocalcaemia519.…”

Section: Discussionmentioning

confidence: 99%

“…With regard to the effect of extracellular calcium, classic in vivo studies showed that low calcium stimulates PTH synthesis and secretion as a result of its short- and long-term effects, and also enhances parathyroid cell proliferation, which is considered a long-term effect15. The effect of low calcium on PTH synthesis and secretion in the acute phase (i.e.…”

Section: Discussionmentioning

confidence: 99%

“…1,25-dihydroxyvitamin D (1,25(OH) 2 D), the active form of vitamin D synthesised from 25-dihydroxyvitamin D (25(OH)D) in the kidney, is a hormone that regulates parathyroid cell proliferation and PTH synthesis not only directly, but also indirectly by increasing the absorption of calcium and phosphate from the intestine4. Calcium and 1,25(OH) 2 D act in co-ordination to suppress PTH gene expression and inhibit parathyroid cell proliferation5.…”

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confidence: 99%

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Persistent fibroblast growth factor 23 signalling in the parathyroid glands for secondary hyperparathyroidism in mice with chronic kidney disease

Kazuki

Takeshita

Furushima

et al. 2017

Sci Rep

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Secondary hyperparathyroidism, in which parathyroid hormone (PTH) is excessively secreted in response to factors such as hyperphosphataemia, hypocalcaemia, and low 1,25-dihydroxyvitamin D (1,25(OH)2D) levels, is commonly observed in patients with chronic kidney disease (CKD), and is accompanied by high levels of fibroblast growth factor 23 (FGF23). However, the effect of FGF23 on the parathyroid glands (PG) remains controversial. To bind to FGF receptors, FGF23 requires αKlotho, which is highly expressed in the PG. Here, we examined the effects of Fgfr1–3, αKlotho, or Fgfr1–4 ablation specifically in the PG (conditional knockout, cKO). When mice with early to mid-stage CKD with and without cKO were compared, plasma concentrations of calcium, phosphate, FGF23, and 1,25(OH)2D did not change significantly. In contrast, plasma PTH levels, which were elevated in CKD mice, were significantly decreased in cKO mice. PG from CKD mice showed augmentation of cell proliferation, which was significantly suppressed by cKO. Parathyroid tissue cultured for 4 days showed upregulation of PTH secretion and cell proliferation in response to FGF23. Both these effects were inhibited by cKO. These findings suggest that FGF23 is a long-term inducer of parathyroid cell proliferation and PTH secretion, and is one cause of secondary hyperparathyroidism in CKD.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Persistent fibroblast growth factor 23 signalling in the parathyroid glands for secondary hyperparathyroidism in mice with chronic kidney disease

Kazuki

Takeshita

Furushima

et al. 2017

Sci Rep

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“…While the major physiological regulator of PTH secretion is the ionized calcium level through interaction with the calcium sensing receptor, PTH secretion is also modulated by serum phosphate, FGF23, and 1,25‐dihydroxyvitamin D 3 (Krajisnik et al . ; Nissenson and Juppner, ). PTH has ostensibly conflicting effects on phosphate homeostasis.…”

Section: Introductionmentioning

confidence: 99%

Regulation of serum phosphate

Lederer

2014

The Journal of Physiology

123

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The regulation of serum phosphate, an acknowledged risk factor for chronic kidney disease and cardiovascular mortality, is poorly understood. The discovery of fibroblast growth factor 23 (FGF23) as a key regulator of renal phosphate handling and activation of vitamin D has revolutionized our comprehension of phosphate homeostasis. Through as yet undetermined mechanisms, circulating and dietary phosphate appear to have a direct effect on FGF23 release by bone cells that, in turn, causes renal phosphate excretion and decreases intestinal phosphate absorption through a decrease in vitamin D production. Thus, the two major phosphaturic hormones, PTH and FGF23, have opposing effects on vitamin D production, placing vitamin D at the nexus of phosphate homeostasis. While our understanding of phosphate homeostasis has advanced, the factors determining regulation of serum phosphate level remain enigmatic. Diet, time of day, season, gender, age and genetics have all been identified as significant contributors to serum phosphate level. The effects of these factors on serum phosphate have major implications for what is understood as 'normal' and for studies of phosphate homeostasis and metabolism. Moreover, other hormonal mediators such as dopamine, insulin-like growth factor, and angiotensin II also affect renal handling of phosphate. How the major hormone effects on phosphate handling are regulated and how the effect of these other factors are integrated to yield the measurable serum phosphate are only now beginning to be studied. AbbreviationsEGFR, epidermal growth factor receptor; FGF23, fibroblast growth factor 23; NHERF1, sodium-hydrogen exchanger regulatory factor isoform 1; PTH, parathyroid hormone; SNP, single nucleotide polymorphism; VDR, vitamin D receptor.

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Upregulation of calcitriol during pregnancy and skeletal recovery after lactation do not require parathyroid hormone

Kirby

Martin

et al. 2013

Journal of Bone and Mineral Research

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Pregnancy invokes a doubling of intestinal calcium absorption whereas lactation programs skeletal resorption to provide calcium to milk. Postweaning bone formation restores the skeleton's bone mineral content (BMC), but the factors that regulate this are not established. We used Pth-null mice to test whether parathyroid hormone (PTH) is required for postweaning skeletal recovery. On a normal 1% calcium diet, wild-type (WT) and Pth-null mice each gained BMC during pregnancy, declined 15% to 18% below baseline during lactation, and restored the skeleton above baseline BMC within 14 days postweaning. A 2% calcium diet reduced the lactational decline in BMC without altering the gains achieved during pregnancy and postweaning. The hypocalcemia and hyperphosphatemia of Pth-null mice normalized during lactation and serum calcium remained normal during postweaning. Osteocalcin and propeptide of type 1 collagen (P1NP) each rose significantly after lactation to similar values in WT and Pth-null. Serum calcitriol increased fivefold during pregnancy in both genotypes whereas vitamin D binding protein levels were unchanged. Absence of PTH blocked a normal rise in fibroblast growth factor-23 (FGF23) during pregnancy despite high calcitriol. A 30-fold higher expression of Cyp27b1 in maternal kidneys versus placenta suggests that the pregnancy-related increase in calcitriol comes from the kidneys. Conversely, substantial placental expression of Cyp24a1 may contribute significantly to the metabolism of calcitriol. In conclusion, PTH is not required to upregulate renal expression of Cyp27b1 during pregnancy or to stimulate recovery from loss of BMC caused by lactation. A calcium-rich diet in rodents suppresses skeletal losses during lactation, unlike clinical trials that showed no effect of supplemental calcium on lactational decline in BMC.

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Parathyroid Hormone

Cited by 18 publications

References 54 publications

Persistent fibroblast growth factor 23 signalling in the parathyroid glands for secondary hyperparathyroidism in mice with chronic kidney disease

Persistent fibroblast growth factor 23 signalling in the parathyroid glands for secondary hyperparathyroidism in mice with chronic kidney disease

Regulation of serum phosphate

Upregulation of calcitriol during pregnancy and skeletal recovery after lactation do not require parathyroid hormone

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