Vitamin D Metabolism and Function

DeLuca, Hector F.

doi:10.1001/archinte.1978.03630300004002

Cited by 91 publications

(43 citation statements)

References 104 publications

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“…The exact mechanism by which vitamin D stimulates calcium transport remains unclear (10). A ma-jor theory holds that 1.25-dihydroxycholecalciferol, the vitamin D metabolite most active in stimulating active calcium transport, acts analogously to other steroid hormones (19).…”

Section: Speculationmentioning

confidence: 99%

Intestinal Calcium-Binding Protein in the Developing Rat Duodenum

Gleason

Lankford

1982

Pediatr Res

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Section: Speculationmentioning

confidence: 99%

Intestinal Calcium-Binding Protein in the Developing Rat Duodenum

Gleason

Lankford

1982

Pediatr Res

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“…One major function ofvitamin D is regulation of the movement of calcium across intestinal epithelium (1)(2)(3)(4). In vitamin D deficiency, the absorption of dietary calcium is substantially reduced; administration of vitamin D or its biologically active metabolites stimulates calcium absorption by means that are not yet completely understood.…”

mentioning

confidence: 99%

Analysis of cytoskeletal proteins and Ca ²⁺ -dependent regulation of structure in intestinal brush borders from rachitic chicks

Howe

Keller

Mooseker

et al. 1982

Proc. Natl. Acad. Sci. U.S.A.

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We have investigated several structural aspects of-the intestinal epithelial brush border from rachitic chicks. At both the light and electron microscope levels, rachitic brush borders are indistinguishable from controls. Although several of the prominent periodic acid-Schiff-positive proteins ofthe brush border membrane have slightly slower mobilities on sodium dodecyl sulfate/polyacrylamide gels than do corresponding proteins from control brush borders, the major components of the microvillus core, including subunits of 105, 95, and 68 roid, and these molecular events appear to involve both protein synthetic and non-protein-synthetic events.Wilson and Lawson (20) reported effects of vitamin D that may specifically involve the cytoskeletal structure of the brush border. They showed that an early response of rachitic chicks to an acute dose of 1,25-dihydroxyvitamin D3 is the increased rate of synthesis of a 42-to 45-kilodalton (kDal) microvillar protein. This protein was later tentatively identified as f3-and yactin (21). Whether there is an increased turnover or de novo synthesis of the actin-like protein had not been clarified. With the assumption that the 42-to 45-kDal protein is bonafide actin, the results of Wilson and Lawson (20,21) are of considerable interest from the standpoint of both the action of 1,25-dihydroxyvitamin D3 on calcium transport and the potential effect of the vitamin D hormone on the structure and behavior of the microvillar cytoskeleton. The role of calcium in the regulation of brush border contractility (22), brush border myosin phosphorylation (23), and the length and bundling of microvillar actin filaments (24-29) has been established. Also, the microvillus contains considerable amounts of calmodulin (30), for which only one function, activation of the' brush border myosin light chain kinase (23), has as yet been defined. Thus, the significance of calcium in the modulation and regulation of the transmural flow of calcium through the intestinal epithelial cell constituted the basis for the present investigation. The main objective was to determine whether vitamin D alters some of the known molecular components of the microvillus cytoskeleton, and thus to provide the basis for further studies on the relationships among the cytoskeleton ofthe brush border, vitamin D, and calcium transport. Other observations on the protein components of the brush border are reported herein. A review of brush border structure and function has recently appeared (31).MATERIALS AND METHODS Animals. White Leghorn cockerels were maintained on a rachitogenic diet (32) in a room with incandescent lighting for 4-5 weeks. Some chicks were injected with 500 international units of vitamin D3 at least 72 hr before the experiments were performed and fed a vitamin D-complete 'diet; these chicks served as vitamin D replete controls. To verify the vitamin D status of animals, radial immunoassays for vitamin D-dependent calcium-binding protein were performed as described (33) on supernates saved from the first...

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“…Since the equimolar EGTA salts infused in both control and experimental periods (group II) obligate identical calcium loads requiring renal excretion, the large increment in urinary calcium excretion is not attributable to chelator infusion, per se. Since both the models of primary PTH excess and secondary PTH excess employed herein would be expected to exhibit large losses of bone calcium and phosphate to ECF, the striking differences between primary and secondary models with respect to the observed magnitude of sustained urinary calcium and phosphate losses, suggest a calcitriol-mediated alteration in gastrointestinal absorption of both ions (1).…”

Section: Discussionmentioning

confidence: 99%

“…A wide variety of experimental evidence in both humans and laboratory animals indicates that the renal mitochondrial metabolite, calcitriol, is the most potent known circulating metabolite of vitamin D and that physiological variation in plasma calcitriol concentration can account, in large part, for the known effects of vitamin D on mineral metabolism in bone, intestine, and extracellular fluid (ECF) (1,2). However, the identities and relative potencies of the individual factors that regulate the steady-state plasma concentration of calcitriol are still unclear.…”

Section: Introductionmentioning

confidence: 99%

Long-term control of plasma calcitriol concentration in dogs and humans. Dominant role of plasma calcium concentration in experimental hyperparathyroidism.

Hulter¹,

Halloran²,

Toto³

et al. 1985

J. Clin. Invest.

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Despite great interest in the elevated circulating levels of calcitriol (1,25[O-12D) associated with the clinical syndrome of human primary hyperparathyroidism, the relative potencies of known and potential stimuli/suppressors of long-term calcitriol levels have not been evaluated in either clinical or experimentally induced hyperparathyroid states. Based on reports that aparathyroid animals exhibit suppressed plasma calcitriol concentration and that acute administration of parathyroid hormone (PTH) to both humans and experimental animals or to renal slices in vitro results in increased plasma calcitriol concentration/production rate, it might be predicted that a chronic experimental model of either hypercalcemic primary hyperparathyroidism or hypocalcemic secondary hyperparathyroidism would show increased plasma calcitriol concentration. Chronic alterations in plasma calcium concentration have not been implicated as modulating calcitriol levels in any species. Accordingly, we investigated the long-term response of plasma calcitriol concentration in states of sustained experimental primary and secondary hyperparathyroidism. Intact dogs (group I) undergoing continuous intravenous PTH infusion for 12 d developed sustained hypercalcemia and hypophosphatemia, and plasma calcitriol concentration decreased from 23±3 to 14±3 pg/ml (P < 0.01). Subsequent chelator (EGTA)-induced chronic normalization of hypercalcemia during ongoing PTH infusion resulted in a large and sustained increase in plasma calcitriol concentration to supernormal levels, reversible during subsequent cessation of chelator infusion. In additional intact dogs (group II), chronic chelator-induced hypocalcemic secondary hyperparathyroidism resulted in a sustained increase in plasma calcitriol concentration despite hyperphosphatemia. In normal human subjects undergoing a 12-13-d continuous intravenous PTH infusion to result in sustained moderate hypercalcemia (12.0±0.2 mg/100 ml) and hypophosphatemia, plasma calcitriol concentration decreased significantly (P < 0.01) as in group I dogs and was followed by reversal to normal levels in a recovery period. The present results provide strong evidence in both humans and dogs that during experimentally induced chronic PTH

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Vitamin D Metabolism and Function

Cited by 91 publications

References 104 publications

Intestinal Calcium-Binding Protein in the Developing Rat Duodenum

Intestinal Calcium-Binding Protein in the Developing Rat Duodenum

Analysis of cytoskeletal proteins and Ca ²⁺ -dependent regulation of structure in intestinal brush borders from rachitic chicks

Long-term control of plasma calcitriol concentration in dogs and humans. Dominant role of plasma calcium concentration in experimental hyperparathyroidism.

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Vitamin D Metabolism and Function

Cited by 91 publications

References 104 publications

Intestinal Calcium-Binding Protein in the Developing Rat Duodenum

Intestinal Calcium-Binding Protein in the Developing Rat Duodenum

Analysis of cytoskeletal proteins and Ca 2+ -dependent regulation of structure in intestinal brush borders from rachitic chicks

Long-term control of plasma calcitriol concentration in dogs and humans. Dominant role of plasma calcium concentration in experimental hyperparathyroidism.

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Analysis of cytoskeletal proteins and Ca ²⁺ -dependent regulation of structure in intestinal brush borders from rachitic chicks