Regulation of Hormone-Sensitive Renal Phosphate Transport

Gattineni, Jyothsna; Friedman, Peter A.

doi:10.1016/bs.vh.2015.01.002

Cited by 16 publications

(14 citation statements)

References 288 publications

(301 reference statements)

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“…PTH stimulates calcitriol synthesis by inducing the expression of CYP27B1 and by suppressing the expression of CYP24A1 [ 54 ]. FGF23 decreases calcitriol levels by suppressing the expression of CYP27B1 and stimulating the expression of CYP24A1 [ 46 , 84 ]. In turn, calcitriol increases FGF23 levels, forming a negative feedback loop.…”

Section: Regulation Of Systemic Phosphate Homeostasismentioning

confidence: 99%

Importance of Dietary Phosphorus for Bone Metabolism and Healthy Aging

Serna

Bergwitz

2020

Nutrients

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Inorganic phosphate (Pi) plays a critical function in many tissues of the body: for example, as part of the hydroxyapatite in the skeleton and as a substrate for ATP synthesis. Pi is the main source of dietary phosphorus. Reduced bioavailability of Pi or excessive losses in the urine causes rickets and osteomalacia. While critical for health in normal amounts, dietary phosphorus is plentiful in the Western diet and is often added to foods as a preservative. This abundance of phosphorus may reduce longevity due to metabolic changes and tissue calcifications. In this review, we examine how dietary phosphorus is absorbed in the gut, current knowledge about Pi sensing, and endocrine regulation of Pi levels. Moreover, we also examine the roles of Pi in different tissues, the consequences of low and high dietary phosphorus in these tissues, and the implications for healthy aging.

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Section: Regulation Of Systemic Phosphate Homeostasismentioning

confidence: 99%

Importance of Dietary Phosphorus for Bone Metabolism and Healthy Aging

Serna

Bergwitz

2020

Nutrients

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“…It adjusts urinary phosphate excretion to balance the quantity of phosphate absorbed in the intestine or the amount stored by cells and bone (3,5,48). The phosphate freely filtered at the glomerulus is mainly (70%-85%) reabsorbed in the renal proximal tubule (PT) through the type 2 sodium/phosphate cotransporters (Npt2a and Np2c), and phosphate regulation in the remainder of the nephron plays only a minor role (5,6,19,34,48,58). Npt2a is expressed in the S1, S2, and S3 segments of apical brush border membranes (BBMs) of superficial and juxtamedullary nephrons with gradually decreasing expression along the PTs, whereas Npt2c is mainly expressed in the S1 segment (3,5,6,19,47).…”

Section: Introductionmentioning

confidence: 99%

“…The phosphate freely filtered at the glomerulus is mainly (70%-85%) reabsorbed in the renal proximal tubule (PT) through the type 2 sodium/phosphate cotransporters (Npt2a and Np2c), and phosphate regulation in the remainder of the nephron plays only a minor role (5,6,19,34,48,58). Npt2a is expressed in the S1, S2, and S3 segments of apical brush border membranes (BBMs) of superficial and juxtamedullary nephrons with gradually decreasing expression along the PTs, whereas Npt2c is mainly expressed in the S1 segment (3,5,6,19,47). Parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23) are two phosphaturic hormones regulating the expression of these transporters (3,5,19).…”

Section: Introductionmentioning

confidence: 99%

“…Npt2a is expressed in the S1, S2, and S3 segments of apical brush border membranes (BBMs) of superficial and juxtamedullary nephrons with gradually decreasing expression along the PTs, whereas Npt2c is mainly expressed in the S1 segment (3,5,6,19,47). Parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23) are two phosphaturic hormones regulating the expression of these transporters (3,5,19). However, their respective roles in regulating renal phosphate reabsorption have not been fully elucidated.…”

Section: Introductionmentioning

confidence: 99%

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In vivo evidence for an interplay of FGF23/Klotho/PTH axis on the phosphate handling in renal proximal tubules

Ide

Rui

Courbebaisse

et al. 2018

American Journal of Physiology-Renal Physiology

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Phosphate homeostasis is primarily maintained in the renal proximal tubules where the expression of sodium/phosphate co-transporters (Npt2a and Npt2c) is modified by the endocrine actions of both FGF23 and PTH. However, the specific contribution of each regulatory pathway in the proximal tubules has not been fully elucidated in vivo. We have previously demonstrated that proximal tubule-specific deletion of the FGF23 co-receptor Klotho results in mild hyperphosphatemia with little to no change in serum levels of FGF23, 1,25(OH)2D3, and PTH. In the present study, we characterized mice in which the PTH receptor PTH1R was specifically deleted from the proximal tubules, either alone or in combination with Klotho (PT-PTH1R-/- and PT-PTH1R/KL-/-, respectively). PT-PTH1R-/- mice showed significant increases in serum FGF23 and PTH levels, whereas serum phosphate levels were maintained in the normal range and Npt2a and Npt2c expression in brush border membrane (BBM) did not change compared with Control mice. In contrast, PT-PTH1R/KL-/- mice displayed hyperphosphatemia and increased abundance of Npt2a and Npt2c in the renal BBM, along with increased circulating FGF23 levels. While, serum calcium was normal, 1,25(OH)2D3 levels were significantly decreased, leading to extremely high levels of PTH. Collectively, mice with a deletion of PTH1R alone in proximal tubules results in only minor changes in phosphate regulation, whereas deletion of both PTH1R and Klotho leads to severe disturbance, including hyperphosphatemia with increased sodium/phosphate co-transporters expression in BBM. These results suggest an important interplay between the PTH/PTH1R and FGF23/Klotho pathways to affect renal phosphate handling in the proximal tubules.

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“…Calcium homeostasis is regulated by parathyroid hormone (PTH), calcitonin, the active form of vitamin D (1α,25-dihydroxyvitamin D (1,25(OH)2D3)), and serum calcium and phosphate levels. Regulation of phosphate metabolism is also important as phosphate is involved in protein and enzyme function, cell signaling, and skeletal mineralization and is a component of cell membranes and nucleic acids [ 2 , 3 ]. The main factors that regulate phosphate homeostasis are PTH, fibroblast growth factor 23 (FGF-23), 1,25(OH)2D3, and Klotho [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

Environmental Factors That Affect Parathyroid Hormone and Calcitonin Levels

Leko

Pleić

Gunjača

et al. 2021

IJMS

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Calciotropic hormones, parathyroid hormone (PTH) and calcitonin are involved in the regulation of bone mineral metabolism and maintenance of calcium and phosphate homeostasis in the body. Therefore, an understanding of environmental and genetic factors influencing PTH and calcitonin levels is crucial. Genetic factors are estimated to account for 60% of variations in PTH levels, while the genetic background of interindividual calcitonin variations has not yet been studied. In this review, we analyzed the literature discussing the influence of environmental factors (lifestyle factors and pollutants) on PTH and calcitonin levels. Among lifestyle factors, smoking, body mass index (BMI), diet, alcohol, and exercise were analyzed; among pollutants, heavy metals and chemicals were analyzed. Lifestyle factors that showed the clearest association with PTH levels were smoking, BMI, exercise, and micronutrients taken from the diet (vitamin D and calcium). Smoking, vitamin D, and calcium intake led to a decrease in PTH levels, while higher BMI and exercise led to an increase in PTH levels. In terms of pollutants, exposure to cadmium led to a decrease in PTH levels, while exposure to lead increased PTH levels. Several studies have investigated the effect of chemicals on PTH levels in humans. Compared to PTH studies, a smaller number of studies analyzed the influence of environmental factors on calcitonin levels, which gives great variability in results. Only a few studies have analyzed the influence of pollutants on calcitonin levels in humans. The lifestyle factor with the clearest relationship with calcitonin was smoking (smokers had increased calcitonin levels). Given the importance of PTH and calcitonin in maintaining calcium and phosphate homeostasis and bone mineral metabolism, additional studies on the influence of environmental factors that could affect PTH and calcitonin levels are crucial.

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Regulation of Hormone-Sensitive Renal Phosphate Transport

Cited by 16 publications

References 288 publications

Importance of Dietary Phosphorus for Bone Metabolism and Healthy Aging

Importance of Dietary Phosphorus for Bone Metabolism and Healthy Aging

In vivo evidence for an interplay of FGF23/Klotho/PTH axis on the phosphate handling in renal proximal tubules

Environmental Factors That Affect Parathyroid Hormone and Calcitonin Levels

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