Regulation of Serum 1α,25-Dihydroxyvitamin D
            <sub>3</sub>
            by Calcium and Phosphate in the Rat

Hughes, Victoria; Brumbaugh, P. F.; Hussler,; Wergedal, J. E.; Baylink, D J

doi:10.1126/science.1188357

Cited by 362 publications

(109 citation statements)

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“…Cholecalciferol is hydroxylated in two steps: the first hydroxylation occurs at the carbon at the 25 position in the liver, and the second hydroxylation takes place in the kidney at the level of the carbon at the 1 position (18) . An increase in the serum levels of 1,25(OH) 2 D 3 by a low-Ca 2þ diet has been shown in human subjects (19) , chicks (20) , ewes (21) and rats (22) , but not in hamsters (23) . On the contrary, dietary Ca 2þ restriction in the presence of constant vitamin D intake may cause depletion of 25-hydroxycholecalciferol, as shown in the plasma of rats as a consequence of high activity of the renal enzyme 25-OH-cholecalciferol 1-hydroxylase (CYP27B1), which catalyses the transformation of 25-hydroxyvitamin D 3 (25OHD 3 ) into 1,25(OH) 2 D 3 (24) .…”

Section: Introductionmentioning

confidence: 99%

Molecular mechanisms triggered by low-calcium diets

et al. 2009

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Ca is not only essential for bone mineralisation, but also for regulation of extracellular and intracellular processes. When the Ca2+ intake is low, the efficiency of intestinal Ca2+ absorption and renal Ca2+ reabsorption is increased. This adaptive mechanism involves calcitriol enhancement via parathyroid hormone stimulation. Bone is also highly affected. Low Ca2+ intake is considered a risk factor for osteoporosis. Patients with renal lithiasis may be at higher risk of recurrence of stone formation when they have low Ca2+ intake. The role of dietary Ca2+ on the regulation of lipid metabolism and lipogenic genes in adipocytes might explain an inverse relationship between dairy intake and BMI. Dietary Ca2+ restriction produces impairment of the adipocyte apoptosis and dysregulation of glucocorticosteroid metabolism in the adipose tissue. An inverse relationship between hypertension and a low-Ca2+ diet has been described. Ca2+ facilitates weight loss and stimulates insulin sensitivity, which contributes to the decrease in the blood pressure. There is also evidence that dietary Ca2+ is associated with colorectal cancer. Dietary Ca2+ could alter the ratio of faecal bile acids, reducing the cytotoxicity of faecal water, or it could activate Ca2+-sensing receptors, triggering intracellular signalling pathways. Also it could bind luminal antigens, transporting them into mucosal mononuclear cells as a mechanism of immunosurveillance and promotion of tolerance. Data relative to nutritional Ca2+ and incidences of other human cancers are controversial. Health professionals should be aware of these nutritional complications and reinforce the dairy intakes to ensure the recommended Ca2+ requirements and prevent diseases.

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Section: Introductionmentioning

confidence: 99%

Molecular mechanisms triggered by low-calcium diets

et al. 2009

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“…Limitations of these earlier reports include 1) relatively insensitive and nonspecific methods of purification of 1,25(OH),D; 2) studies restricted to animals subjected to vitamin D-deficient diets; 3) use of media calcium concentrations in supraphysiologic millimolar ranges; and 4) inconsistencies in the methods and results among the various reports. For example, several studies demonstrated that Open columns, mitochondria incubated without calcium; hatched columns, mitochondria incubated with calcium.…”

Section: Discussionmentioning

confidence: 99%

Media Calcium Attenuates Mitochondrial 1,25(OH)2D Production in Phosphorus or Vitamin D-Deprived Rats

Carpenter

Ellis

1995

Pediatr Res

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Although PTH and hypophosphatemia are the best known stimulators of 25-hydroxyvitamin D-la-hydroxylase, 1,25(OH),D3 production in rats and humans can be modulated by circulating calcium, independent of PTH. To test whether calcium modulates this function directly in mitochondria, we examined effects of calcium on la-hydroxylase in isolated mitochondrial preparations under basal and stimulated conditions. Rats were fed a low phosphorus (or matched control) diet for 4 or 7 d or a vitamin D-deficient (or matched control) diet for 2, 4, or 7 wk. Renal mitochondria were isolated and assayed for la-hydroxylase activity in the presence or absence of added calcium. Calcium did not alter la-hydroxylase in rats on control diets. After 4 d of low phosphorus diet, la-hydroxylase was increased 2-fold over basal activity; media calcium prevented this stimulatory response. By 7 d the calcium effect was not evident. After 4 wk of vitamin D deprivation, activity was -30-fold greater than controls; calcium reduced this response significantly (15-fold). A significant, but less marked inhibition of activity by calcium was present in rats subjected to 7 wk of vitamin D deprivation. Extramitochondrial calcium can directly modulate 1,25(OH),D3 production, but this effect appears to be secondary to the primary physiologic regulators of this function. The calcium effect can be overcome after longer term exposure to phosphorus deprivation, but is sustained in the presence of long term vitamin D deprivation. The best known active metabolite of vitamin D is 1,25(OH),D, which in humans and other mammals, effects numerous physiologic events. Production of 1,25(OH),D is tightly controlled at the final step of its biosynthetic pathway, performed in renal tubular mitochondria by a P450 enzyme system, the renal la-OHase (1). Although several factors have been shown to be trophic for this reaction (e.g. IGF-I, estrogen, thyroid hormone, calcitonin), the predominant physiologic regulators of this reaction in the intact organism are hypophosphatemia and PTH (2). The stimulatory effect of hypocalcemia on 1,25(OH),D production has generally been attributed to resultant secondary hyperparathyroidism (3). In contrast with the view that calcium regulation of la-OHase is entirely dependent on PTH effects, more recent work has shown that extracellular calcium is able to regulate this reaction in rats (4, 5) and humans (6) finding, we examined the ability of calcium to modulate I ) basal enzyme activity and 2) stimulated enzyme activity (using two standard dietary provocations) directly at the mitochondrial level. METHODS Animals.Male Holtzman rats were obtained from Harlan (Madison, WI) at weanling. In experiments examining effects of phosphorus deprivation, rats were housed in our animal facilities and placed on either a low phosphorus diet (Teklad, Madison, WI), containing 0.02% phosphorus, 0.6% calcium and 2200 U of vitamin D/kg, or a control diet containing 0.6% phosphorus, and otherwise matched to the experimental diet.Animals were killed after 4 or...

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“…Evidence that the same relationships may exist in man comes from recent measurements of 1,25(OH)2CC in plasma which indicate that the levels are higher than normal in hyperparathyroidism and lower than normal in hypoparathyroidism (Hughes et al, 1975). They are also low in renal failure (Mawer et al, 1973) perhaps because renal mass is diminished or as a result of the hyperphosphaternia that exists in this condition.…”

Section: Regulation Of Calcium Metabolism 523mentioning

confidence: 92%

“…It is possible that the effects of vit D on bone mineralisation are secondary to changes in extracellular fluid concentrations of calcium and phosphate, but this explanation may be too simple to account for all the experimental and clinical observations. Unfortunately, there are no good experimental systems for studying skeletal mineralisation in vitro and the major effect of There is evidence that the effect of calcium deprivation in increasing 1,25(OH)2CC is mediated by increased secretion of PTH, whereas the effect of phosphate restriction is independent of PTH (Hughes et al, 1975).…”

Section: Regulation Of Calcium Metabolism 523mentioning

confidence: 99%

Regulation of Calcium Metabolism

Russell

1976

Ann Clin Biochem

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This paper reviews the regulation of calcium metabolism in man. The body's calcium economy is determined by the relationship between the intestinal absorption of calcium, the renal handling of calcium, and by the movements of calcium in and out of the skeleton. These processes are influenced by many factors, the most important of which are parathyroid hormone and the hormones derived from the renal metabolism of vitamin D, notably l,25-dihydroxyvitamin D aThe role of endogenous calcitonin in man is still controversial, but there are severalother hormones which have some influence on calcium metabolism, including thyroid hormone, growth hormone, and the adrenal and gonadal steroids. Clinical disorders of calcium metabolism and their treatment are discussedin terms of the disturbances in normal physiologythey represent.There has been a rapid growth in knowledge about calcium metabolism in the past decade, particularly in understanding the biochemistry of the calciumregulating hormones. This recent work has meant that many old concepts have had to be re-examined, a process which is still far from complete, especially in relation to human disease. The purpose of this paper is to review current concepts in outline and to refer the reader to other sources for more detailed information (see Bibliography).Regulation of calcium metabolism can be considered from at least three distinct but interrelated aspects: (i) control of the concentration of calcium in extracellular fluid and tissues; (ii) control of the body's overall calcium balance, i.e., the relationship between gains and losses; (iii) control of the shape, structure and composition of bone and the way these respond to changes in external factors such as load bearing. ·From Widdowson and Dickerson (1964). DISTRIBUTION OF CALCIUM AND PHOSPHATEis outside the skeleton, the remainder within it. This Most of the body's calcium resides within bone exchangeable pool of calcium is very important in (Table 1). The other major inorganic constituent homoeostasis, and movements of calcium ions beof bone is phosphorus, as inorganic phosphate (Pi). tween body fluids. cells, and the surfaces of bone Unlike calcium, the concentration of which is low occur continuously. Between 1 and 4 %of the human in most soft tissues, about 15 % of the body's adult skeleton is thought to be renewed each year.phosphorus lies outside the skeleton, in body fluids Trabecular bone has a faster turnover than cortical and in tissues, mostly as organic phosphate com-bone. pounds, e.g., nucleic acids and nucleotides, phosphoIn order to understand the way in which the body lipids and phosphorylated metabolites.gains and loses calcium from the external environStudies with radioisotopes (45Ca and 47Ca) have ment and the way in which internal control is shown that in normal human adults the exchangeable achieved the system can be simplified to a considerapool of calcium represents less than 1 % of total tion of the roles of the three major organs involved, body calcium (in the region of 70 mg/kg during the...

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Regulation of Serum 1α,25-Dihydroxyvitamin D ₃ by Calcium and Phosphate in the Rat

Cited by 362 publications

References 18 publications

Molecular mechanisms triggered by low-calcium diets

Molecular mechanisms triggered by low-calcium diets

Media Calcium Attenuates Mitochondrial 1,25(OH)2D Production in Phosphorus or Vitamin D-Deprived Rats

Regulation of Calcium Metabolism

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Regulation of Serum 1α,25-Dihydroxyvitamin D 3 by Calcium and Phosphate in the Rat

Cited by 362 publications

References 18 publications

Molecular mechanisms triggered by low-calcium diets

Molecular mechanisms triggered by low-calcium diets

Media Calcium Attenuates Mitochondrial 1,25(OH)2D Production in Phosphorus or Vitamin D-Deprived Rats

Regulation of Calcium Metabolism

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Regulation of Serum 1α,25-Dihydroxyvitamin D ₃ by Calcium and Phosphate in the Rat