Parathyroid hormone gene expression in hypophosphatemic rats.

Kilav, Rachel; Silver, Justin; Naveh-Many, Tally

doi:10.1172/jci118038

Cited by 182 publications

(105 citation statements)

References 36 publications

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“…Several in vitro (20)(21)(22) and in vivo (23)(24)(25) studies have demonstrated that phosphorus administration can stimulate PTH secretion independently of calcium levels, which was in accordance with our results.…”

Section: Resultssupporting

confidence: 93%

Oral Phosphorus Supplementation Secondarily Increases Circulating Fibroblast Growth Factor 23 Levels at Least Partially via Stimulation of Parathyroid Hormone Secretion

Takasugi

Akutsu

Nagata

2014

J Nutr Sci Vitaminol

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Phosphorus is an essential nutrient for many biological functions, including cellular signal transduction, mineral metabolism, and energy exchange. On the other hand, a relatively high serum phosphorus level is reportedly a risk factor for cardiovascular disease (1, 2) because inorganic phosphates have been shown to stimulate differentiation of vascular smooth muscle cells into calcifying vascular cells (3). Therefore, serum phosphorus regulation may help to prevent cardiovascular diseases.Fibroblast growth factor 23 (FGF23) is a bone-derived hormone that plays a regulatory role in phosphorus homeostasis. FGF23 has been shown to reduce serum phosphorus levels by inhibition of proximal tubular phosphorus reabsorption through decreased expression of types 2a and 2c sodium-phosphate cotransporters and by decreasing intestinal phosphorus absorption through inhibiting calcitriol synthesis in the kidney (4). Moreover, FGF23-null mice were shown to exhibit severe vascular calcification with concomitant hyperphosphatemia (5). These facts suggest that FGF23 may have a protective effect on vascular calcification by hyperphosphatemia suppression. In contrast, several hemodialysis studies reported that elevated FGF23 levels were associated with aortic calcification (6) and mortality (7, 8) independent of serum phosphorus levels. Elevated serum FGF23 levels, even within the normal range, are reportedly associated with increased left ventricular mass index and increased risk for the presence of left ventricular hypertrophy in elderly subjects (9). Furthermore, a recent study suggested that elevated FGF23 levels contributed directly to high rates of left ventricular hypertrophy and mortality in individuals with chronic kidney diseases (10). Thus, FGF23 regulation may also play a clinically significant role in the prevention of cardiovascular diseases.Oral phosphorus supplementation is known to stimulate FGF23 secretion, although the underlying mechanism has not been clarified. In our preliminary study, we found that plasma FGF23 levels in rats increased after oral phosphorus administration at a physiological dose; however, this increase slowly began around the time that plasma phosphorus levels had decreased (unpublished data). Based on these findings, we reasoned that oral phosphorus supplementation may secondarily increase FGF23 secretion. Parathyroid hormone (PTH) is also secreted in response to phosphorus administration (11) and subsequently increases urinary phosphorus excre- Note Oral Phosphorus Supplementation Secondarily Increases Circulating Fibroblast Growth Factor 23 Levels at Least Partially via Stimulation of Parathyroid Hormone SecretionSatoshi Takasugi, Miho Akutsu and Masashi Nagata Food Science Research Laboratories, Division of Research and Development, Meiji Co., Ltd., 540 Naruda, Odawara, Kanagawa 250-0862, Japan (Received August 20, 2013) Summary Oral phosphorus supplementation stimulates fibroblast growth factor 23 (FGF23) secretion; however, the underlying mechanism remains unclear. The aim of this ...

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Section: Resultssupporting

confidence: 93%

Oral Phosphorus Supplementation Secondarily Increases Circulating Fibroblast Growth Factor 23 Levels at Least Partially via Stimulation of Parathyroid Hormone Secretion

Takasugi

Akutsu

Nagata

2014

J Nutr Sci Vitaminol

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“…Figure 5A shows that 1,25(OH) 2 D 3 administration in mice significantly increased renal mRNA levels of Stc2 by 160% and decreased renal Cyp27b1 mRNA levels by 5%, compared with control vehicle mice. It has been reported that serum PTH protein and mRNA levels are decreased by a low-phosphate diet (Kilav et al 1995). Therefore, we fed rats a low-phosphate diet for 3 days, followed by treatment with PTH.…”

Section: Downregulation Of Stc2 Mrna Expression By Pthmentioning

confidence: 99%

Stanniocalcin 2 is positively and negatively controlled by 1,25(OH)2D3 and PTH in renal proximal tubular cells

Takei¹,

Yamamoto²,

Masuda³

et al. 2009

Journal of Molecular Endocrinology

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We have previously identified a second mammalian stanniocalcin (STC2) in humans and demonstrated that STC2 inhibits phosphate uptake in an opossum renal proximal tubular cell line (opossum kidney (OK) cells). However, the regulation of Stc2 gene expression in OK cells is not well understood. In this study, we identified the opossum Stc2 cDNA sequence. The opossum STC2 amino acid sequence had 78 . 8% homology with human STC2, and has a conserved putative N-linked glycosylation site. Next, we investigated the regulation of Stc2 gene expression by the classical calcium and phosphate-regulating factors 1,25(OH) 2 D 3 and PTH in OK cells. In western blot analysis using affinity-purified anti-STC2 antibody, the secretion of STC2 protein was stimulated by 1,25(OH) 2 D 3 in a dose-dependent manner. By contrast, PTH suppressed the induction of STC2 protein secretion by 1,25(OH) 2 D 3 . Real-time PCR analysis revealed that Stc2 mRNA expression was increased by 1,25(OH) 2 D 3 in a dose-and time-dependent manner. In addition, actinomycin D, an RNA synthesis inhibitor, prevented the effects of 1,25(OH) 2 D 3 on Stc2 gene expression. On the other hand, PTH and phorbol 12,13-myristic acetate, a specific PKC activator, but not 8-bromo-cyclic AMP, a specific PKA activator, reduced the mRNA levels of Stc2. In addition, Gö 6976, a specific PKC inhibitor, abolished the downregulation of Stc2 mRNA expression by PTH. Furthermore, we demonstrated that the renal Stc2 mRNA expression was increased by 1,25(OH) 2 D 3 and decreased by PTH in vivo. These results suggest that STC2 is positively and negatively controlled by 1,25(OH) 2 D 3 and PTH in renal proximal tubular cells.

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“…A high-phosphate diet has also been shown to increase prepro-PTH mRNA independent of calcium and calcitriol in normal rats (42). Besides an effect on resistance to the calcemic action of PTH, there is in vitro evidence that phosphorus directly stimulates PTH secretion in intact rat parathyroid glands or slices of hyperplastic human parathyroid glands (45)(46)(47)(48)(49). Finally, in hemodialysis patients, high serum phosphorus has been shown to interfere with suppression of PTH by serum calcium (50).…”

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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Parathyroid hormone gene expression in hypophosphatemic rats.

Cited by 182 publications

References 36 publications

Oral Phosphorus Supplementation Secondarily Increases Circulating Fibroblast Growth Factor 23 Levels at Least Partially via Stimulation of Parathyroid Hormone Secretion

Oral Phosphorus Supplementation Secondarily Increases Circulating Fibroblast Growth Factor 23 Levels at Least Partially via Stimulation of Parathyroid Hormone Secretion

Stanniocalcin 2 is positively and negatively controlled by 1,25(OH)2D3 and PTH in renal proximal tubular cells

Dynamics of Parathyroid Hormone Secretion in Health and Secondary Hyperparathyroidism

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