Resistance to the Phosphaturic and Calcemic Actions of Parathyroid Hormone during Phosphate Depletion

Gloor, Hans-Jakob; Bonjour, J. P.; Caverzasio, Joseph; Fleisch, H.

doi:10.1172/jci109312

Cited by 44 publications

(8 citation statements)

References 26 publications

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“…A decrease in the PTH phosphaturic capacity may be considered to be an associated factor, as described in previous works . A decrease in Pi intake may be also considered because it is known that Pi deprivation produces PTH resistance without altering the cAMP excretion (Gloor et al 1979). We have reported a diminution in the excretion of cAMP in the urine of Altreated rats .…”

Section: Discussionmentioning

confidence: 99%

Effects of aluminum on phosphate metabolism in rats: a possible interaction with vitamin D3 renal production

et al. 2004

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The effect of chronic aluminum (Al) administration on the phosphorous (Pi) metabolism of different target tissues was studied. Male Wistar rats received aluminum lactate for 3 months (5.75 mg/kg bodyweight of Al, i.p., three times per week). The animals were studied at the end of the 1st, 2nd and 3rd month of treatment. They were housed individually in metabolic cages for 4 days to study Pi and calcium (Ca) balance. Daily food and water intakes were recorded for all animals and urine and feces were collected for Pi and calcium assays. After 3 months the Pi intestinal absorption and the Pi deposition in bone were studied using 32Pi. Another group of rats was treated daily for 7 days with calcitriol (0.08 microg/kg body weight in sesame oil, i.p.) and the Pi balance was studied for the last 4 days. The results indicated that chronic administration of Al affected simultaneously the Pi and calcium balance, with a significant diminution of calcium and increased Pi accretion in bones, together with a diminution in the intestinal absorption of Pi. The treatment of the rats with calcitriol promoted a normalized Pi balance in Al treated rats. These findings suggest that Al could modify the Pi metabolism acting directly on intestine, kidney and bone, or indirectly through possible changes in the levels of vitamin D3.

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Section: Discussionmentioning

confidence: 99%

Effects of aluminum on phosphate metabolism in rats: a possible interaction with vitamin D3 renal production

et al. 2004

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“…Moreover, our preliminary findings lead us first to propose that the physiologic role of FGF23 is to act as a counterregulatory hormone for 1,25(OH) 2 effect would be to increase renal phosphate clearance under circumstances in which phosphate was not needed for mineralization of extracellular matrix. Second, 1,25(OH) 2 D 3 stimulation of FGF23 production by osteoblasts in bone provides a mechanism to maintain phosphate homeostasis in the setting of suppressed PTH secretion (41). In the presence of 1,25(OH) 2 D 3 stimulation of calcium and phosphate absorption by the gastrointestinal tract (42), increments in calcium (as well as 1, 25[OH] 2 D 3 itself) act on the parathyroid gland to suppress PTH, thereby limiting the ability of the kidney to excrete the increased phosphate absorbed from the gastrointestinal tract.…”

Section: Discussionmentioning

confidence: 99%

Fibroblast Growth Factor 23 Is a Counter-Regulatory Phosphaturic Hormone for Vitamin D

Liu

Tang

Zhou

et al. 2006

Journal of the American Society of Nephrology

594

485

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The regulation of the phosphaturic factor fibroblast growth factor 23 (FGF23) is not well understood. It was found that administration of 1,25-dihydroxyvitamin D 3 (1,25[OH] 2 D 3 ) to mice rapidly increased serum FGF23 concentrations from a basal level of 90.6 ؎ 8.1 to 213.8 ؎ 14.6 pg/ml at 8 h (mean ؎ SEM; P < 0.01) and resulted in a four-fold increase in FGF23 transcripts in bone, the predominate site of FGF23 expression. In the Hyp-mouse homologue of X-linked hypophosphatemic rickets, administration of 1,25(OH) 2 D 3 further increased circulating FGF23 levels. In Gcm2 null mice, low 1,25(OH) 2 D 3 levels were associated with a three-fold reduction in FGF23 levels that were increased by administration of 1,25 ( FGF23 also suppresses 1␣ hydroxylase activity in the proximal renal tubule, leading to reduced circulating levels of 1,25(OH) 2 D 3 (2,10,14,15). The significance of FGF23 regulation of 1,25(OH) 2 D 3 production is not clear, but the findings that FGF23 is produced predominantly by osteoblasts in bone and that FGF23 regulates phosphate reabsorption and 1,25(OH) 2 D 3 production by the kidney raise the possibility that FGF23 may be involved in a bone-kidney axis that controls phosphate and vitamin D homeostasis (16,17). How FGF23 is integrated with the vitamin D-parathyroid hormone (PTH) axis, which plays a central role in calcium homeostasis, skeletal development, and mineralization (18), however, is not clear. Understanding the effects of 1,25(OH) 2 D 3 on FGF23 production is important, because vitamin D therapy often is used to treat FGF23-mediated hypophosphatemic disorders, such as XLH (19).In an effort to understand more fully the regulation of FGF23 expression in osteoblasts and bone, we assessed the effect of 1,25(OH) 2 D 3 administration on circulating levels of FGF23 in wild-type Gcm2 null (20) and Hyp mice (21), as well as the effects of 1,25(OH) 2 D 3 on the FGF23 transcripts in bone. In addition, we investigated the ability of 1,25(OH) 2 D 3 to regulate endogenous FGF23 transcripts and the activity of a transfected murine FGF23 promoter luciferase reporter in osteoblasts. Our findings demonstrate the importance of bone as a target for vitamin D-mediated increments in FGF23 production and suggest that FGF23 production serves as a counterregulatory hormone to enhance renal phosphate clearance in response to vitamin D-mediated increments in gastrointestinal phosphate absorption and decrements in the phosphaturic hormone PTH. Materials and Methods 1,25(OH) 2 D 3 and PTH AdministrationBoth Hyp mice (21) and C57BL/6J mice were purchased from Jackson Laboratory (Bar Harbor, ME). Male and female Gcm2 ϩ/Ϫ mice were mated to generate homozygous Gcm2 null mice that lacked parathyroid glands (22). All mice were maintained and used in accordance with recommendations in

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“…It has been reported that phosphate depletion is associated with hypercalciuria (25,26) and with resistance to the actions of PTH to stimulate tubular reabsorption of calcium (25), to inhibit tubular reabsorption of phosphate (27), and to raise serum calcium (28). The hypercalciuria in phosphate depletion has been attributed to the increase in the filtered load of calcium, which is due to accompanying hypercalcemia, and to the decrease in the tubular reabsorption, which is due to functional hypoparathyroidism (25,29).…”

Section: And 2)mentioning

confidence: 99%

Vitamin D deficiency and renal calcium transport in the rat.

Yamamoto¹,

Kawanobe²,

Takahashi³

et al. 1984

J. Clin. Invest.

129

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A bstract. To examine the role of vitamin D in the renal tubular handling of calcium, clearance studies were performed in three groups of rats: group A rats fed a standard vitamin D-deficient diet (Ca 0.45%, P 0.3%) for 6 wk, were hypocalcemic with secondary hyperparathyroidism; group B rats fed the same diet as in group A but with high calcium (Ca 1.4%) and 20% lactose, were normocalcemic and without secondary hyperparathyroidism; group C rats fed the same diet as in group A but supplemented with 25 U of vitamin D3 orally twice a week, were normocalcemic, vitamin D-replete, and euparathyroid. After thyroparathyroidectomy (TPTX), each rat was infused intravenously with an electrolyte solution that contained a fixed concentration of calcium (0-30 mM) with or without parathyroid hormone (PTH; 0.75 or 2.5 U/h) at a rate of 3 ml/h. Urinary calcium excretion and serum calcium concentrations were measured between 16 and 19 h of the infusion, and the apparent threshold of calcium excretion was determined.The threshold of calcium excretion was lower in vitamin D-deficient TPTX rats (groups A and B) than in vitamin D-replete TPTX rats (group C), and not different between group A and group B. Administration of PTH at a dose of 0.75 U/h increased the threshold of calcium excretion by -0.6 mM in group C, but did not alter the threshold either in group A or group B. Administration

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Resistance to the Phosphaturic and Calcemic Actions of Parathyroid Hormone during Phosphate Depletion

Abstract: A B S T R A C T Recent observations indicate that in thyroparathyroidectomized (TPTX) rats fed a low (0.2 gll00 g) phosphorus diet, the tubular phosphaturic response to parathyroid hormone (PTH)

Cited by 44 publications

References 26 publications

Effects of aluminum on phosphate metabolism in rats: a possible interaction with vitamin D3 renal production

Effects of aluminum on phosphate metabolism in rats: a possible interaction with vitamin D3 renal production

Fibroblast Growth Factor 23 Is a Counter-Regulatory Phosphaturic Hormone for Vitamin D

Vitamin D deficiency and renal calcium transport in the rat.

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