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At least 217 records · Page 12Linked to original sources
PubMed1986

25-Hydroxyvitamin D3 metabolism in a human leukemia cell line.

1,25-dihydroxyvitamin D3 (1,25(OH)2D3) is a potent inducer of monocytic differentiation of the human promyelocytic leukemia cell line, HL-60. We have noted that 25-hydroxyvitamin D3 (25(OH)D3) in high doses is also capable of promoting monocytic differentiation of this cell line. To test the possibility that the latter activity is due to conversion of 25OHD3 to 1,25(OH)2D3 by HL-60, we exposed HL-60 cells to 25OHD3 and analyzed the products by HPLC and radioreceptor assay. When chromatographed in the traditional solvent system (isopropanol-hexane), a new peak appears which migrates with authentic 1,25(OH)2D3. However, in a solvent system containing dichloromethane, 90% of the peak migrates with another metabolite, 19-Nor-10-Keto-25OHD3 (19-Nor-25OHD3). Production of this metabolite is enhanced by living cells and is synthesized by both virgin HL-60 and those which have undergone differentiation. We next determined if authentic 19-Nor-25OHD3 also promotes differentiation of this cell. As assessed by appearance of the monocyte-specific surface antigen (63D3) and macrophage-specific esterase activity, we find that this metabolite does, in fact, induce monocytic differentiation of HL-60 with a potency of approximately 1/200 that of 1,25(OH)2D3 and similar to that of 25OHD3. In agreement with the effect upon cell maturation, 19-Nor-25OHD3 displaces 3H-1,25(OH)2D3 from its HL-60 receptor with an efficiency comparable to 25OHD3. Hence, HL-60 cells convert 25OHD3 to 19-Nor-25OHD3, and 19-Nor-25OHD3 induces monocytic differentiation of HL-60 with comparable efficiency to its precursor, 25OHD3.

Calcifediol↗
PubMed1987

Effect of aging on vitamin D stores and bone density in women.

It has been suggested that the decrease in vitamin D stores with aging is a contributory cause of age-related osteoporosis. We studied this question by measuring bone mineral density (BMD) of the mid-radius, distal radius, and lumbar spine assessed by single and dual photon absorptiometry in 122 women, aged 33-94 years, selected from a random sample of Rochester, MN residents. We measured serum 25-hydroxyvitamin D (25OHD), the major storage form of vitamin D, as well as 25OHD3 (representing both endogenous and exogenous sources of vitamin D), and 25OHD2 (representing only exogenous sources). Both baseline serum total 25OHD (r = -0.29, P less than 0.001) and the metabolite 25OHD3 (r = -0.41, P less than 0.001), were negatively associated with age at baseline. After adjusting for the effect of age by multiple regression analysis, there was no association between serum levels of 25OHD2, 25OHD3, or total 25OHD and BMD for any of the three skeletal scanning sites. Thus, in a northern American population we cannot demonstrate that reduced bioavailability of vitamin D plays a major role in age-related bone loss.

25-Hydroxyvitamin D 2↗
PubMed1987

Influence of nutritional factors on calcium-regulating hormones and bone loss.

UNLABELLED: The relationships between nutritional factors, calcium regulating hormones, and bone density were evaluated in three groups of normal subjects in rural southeast Kansas. Dietary intake of calcium (Ca), phosphorous (P), protein, and vitamin D; and serum 25OHD, Ca, P, parathyroid hormone (iPTH), and bone density (distal 1/3 radius) were measured in 29 elderly women, 35 elderly men, and 50 perimenopausal women. Measurements were repeated 5 years and 4 years later respectively in 16 elderly women and 15 elderly men. The r values for significant regression correlations for each group were as follows: perimenopausal: bone density and dietary Ca:P--r = .29, iPTH and 25OHD--r = -.38; elderly women: 25OHD and dietary Vitamin D(D)--r = .58, change in bone density (delta BD) and initial bone density (BDI)--r = -.71, delta BD and serum 25OHD--r = -.60, serum calcium and age--r = -.42; elderly men: Serum 25OHD and D--r = .61, iPTH and 25OHD--r = -.43, iPTH and serum phosphorous--r = .59. CONCLUSIONS: The more adequate the state of vitamin D nutriture, the lower the serum iPTH in perimenopausal women and elderly men and the less bone loss in elderly women. The Ca:P ratio in the diet may be important in maintaining bone density in perimenopausal women.

Adult↗
PubMed1986

Bone in the marmoset: a resemblance to vitamin D-dependent rickets, type II.

The common marmoset, a New World monkey, requires a large amount of vitamin D3 to maintain its normal growth. This monkey is reported to have an end-organ resistance to 1 alpha,25-dihydroxyvitamin D3 (1 alpha,25(OH)2D3). In this study, the bone morphology of marmosets fed a high vitamin D3 diet (intake of vitamin D3, 110 IU/day/100 g of body weight) was compared by X-ray and histological examinations with that of rhesus monkeys (Old World monkey) fed a normal diet (intake of vitamin D3, 5 IU/day/100 g of body weight). Three of 20 marmosets were found by X-ray examination to have osteomalacic changes in their bones despite the high daily intake of vitamin D3, whereas none of the 5 rhesus monkeys showed any signs of osteomalacia. Osteomalacic marmosets had distinct increases in osteoid surface, relative osteoid volume, and active osteoclastic bone resorption, whereas non-osteomalacic marmosets had no increase in osteoid tissues in their bones. None of the marmosets, either osteomalacic or non-osteomalacic, was hypercalcemic despite the extremely high circulating levels of 1 alpha,25(OH)2D3. However, the serum 25-hydroxyvitamin D3 (25OHD3) and 24R,25-dihydroxyvitamin D3 (24R,25(OH)2D3) levels were significantly lower in the osteomalacic than in the non-osteomalacic marmosets. These results suggest that the marmoset is likely to exhibit osteomalacic bone changes despite the high daily intake of vitamin D3. These changes resemble those in vitamin D-dependent rickets, type II.

24,25-Dihydroxyvitamin D 3↗
PubMed1991

The relationship between serum vitamin D concentrations and in vivo tetracycline labeling of osteoid in crush fracture osteoporosis.

Twenty of 22 consecutive British patients with crush fracture osteoporosis had transiliac bone biopsies following double in vivo tetracycline labeling synchronized with the collection of serum for the measurement of vitamin D metabolites. A significant but direct (rather than inverse) relationship was found between 25-hydroxyvitamin D (calcidiol) levels and the fraction of cancellous surfaces covered with osteoid not taking either tetracycline label (r = 0.53, P less than 0.02). There was no correlation with 1,25-dihydroxyvitamin D levels. No patient had frankly thickened osteoid seams although 3 had reduced but measurable calcidiol levels. These results make it unlikely that the majority of patients with osteoporosis who have osteoid of normal thickness but reduced uptake of tetracycline have a mineralization defect secondary to vitamin D deficiency. The pathophysiological significance of unlabeled osteoid in osteoporosis requires further investigation.

Aged↗
PubMed1989

Vitamin D deficiency in the chick embryo: effects on prehatching motility and on the growth and differentiation of bones, muscles, and parathyroid glands.

Vitamin D-deficient chicken embryos were obtained by feeding laying hens diets in which 3-7 micrograms calcitriol replaced the vitamin D3 supplement. A large proportion of the D-deficient embryos failed to complete the prehatching positional changes required to start pulmonary respiration. For this reason most of them became cyanotic and had subcutaneous edema and hemorrhages in the head and neck and died without hatching. Total as well as leg-bone and muscle weights were significantly lower in the deficient embryos than in the controls and these changes probably explain the inability of the embryos to complete the movements required to place the beak in contact with the air chamber and start pulmonary respiration. The histological study of the tibiae showed decreased mineralization with narrower trabeculae and enlarged osteoid seams; bone resorption at the inner surface was also significantly decreased. The ultrastructural study of parathyroid glands showed increased functional activity reflected by increased number and size of cisternae of rough endoplasmic reticulum. Injection of 10 ng calcitriol, 1 microgram 24,25-(OH)2D3, or 2 micrograms 25OHD3 to deficient embryos on the 14th day of incubation improved hatchability, bone and muscle weights, and both bone mineralization and resorption.

24,25-Dihydroxyvitamin D 3↗
PubMed1987

Effects of long-term maintenance therapy with a new glucocorticoid, deflazacort, on mineral metabolism and statural growth.

Deflazacort was substituted for Prednisone (based on the equivalence 1 mg Prednisone equals 1.2 mg Deflazacort), during maintenance glucocorticoid therapy in 9 children, 5 with renal diseases and 4 with connective tissue or immunoproliferative disorders. Six patients received 0.26-0.35 mg/kg body weight (B.W.)/day and 3 0.48-1.2 mg/kg B.W. on alternate days, for 10-16 months. Except for a child with chronic juvenile arthritis, who was also unresponsive to Prednisone, the therapeutic effects of Deflazacort were excellent. Steroid side effects present in 8 patients decreased or disappeared. Plasma Ca, P, Mg, creatinine, alkaline phosphatase, iPTH(1-34), urinary excretion of Ca, cAMP, and TRP remained normal. Plasma iPTH(1-84) remained normal in 5 children; in the other 4 patients it increased from normal to slightly elevated values. On Deflazacort, plasma calcidiol concentrations were within the normal range in 6/8 patients prescribed daily doses of vitamin D2 (1,600-2,400 IU) or calcidiol (20 micrograms). Plasma 1,25(OH)2D levels monitored in 5 children were also normal. The osteoporosis, evaluated on the tibial cortico-diaphyseal ratio and the trabecular aspect of bone radiograms, present in 5 patients, persisted in 1 and improved in the others. On Deflazacort, statural growth proceeded normally in all subjects, with a modest acceleration of growth velocity in 3 children. These results seem encouraging for extending clinical trials with Deflazacort to the active phase of pediatric diseases requiring glucocorticoid.

Adolescent↗
PubMed1986

Stimulation of undermineralized matrix formation by 1,25 dihydroxyvitamin D3 in long bones of rats.

We previously reported that pharmacologic doses of 1,25 dihydroxyvitamin D3 (1,25(OH)2D3) given for 2-3 days, inhibited osteoblastic collagen synthesis in young rats. In this study, we tested the effects of 5, 25, and 125 ng of 1,25(OH)2D3 injected subcutaneously into 6-week-old rats for 12 or 18 days. In rats given 125 ng, cortical bone of distal half femurs exhibited decreased calcium (Ca) content but dry weight and hydroxyproline (Hyp) content were no different from control. Trabecular bone Ca was not different from control but dry weight and Hyp were increased. When cortical and trabecular bone were combined, there was a decrease in Ca, an increase in Hyp, and a 50% decrease in Ca:Hyp. Fluorescent labels given after 8 days of treatment were either diffuse or absent in calcified sections from rats given 125 ng, indicating impaired mineralization. The 25 and 125 ng doses produced hypercalcemia with normal serum phosphate. There was a dose-related increase in serum immunoreactive bone gla protein (BGP) and serum 1,25(OH)2D3 and a decrease in serum 25(OH)D3. At the 5 ng dose, no adverse effects were seen on body growth. With 25 ng and 125 ng, growth was inhibited. Increased serum urea nitrogen and histologic evidence of nephrocalcinosis occurred at the 125 ng dose. When 125 ng was given for 12 days and then withdrawn for 6 days, systemic toxicity decreased and bone Hyp and Ca increased so that Ca:Hyp remained low and comparable to that of rats treated with 1,25(OH)2D3 continuously.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Topical administration of 1,25-dihydroxyvitamin D3 for psoriasis: report of five cases.

The effects of topical administration of 1,25-dihydroxyvitamin D3, as 0.1 and 0.5 microgram per g base, and control base applied to contralateral skin lesions in five patients with persistent psoriasis were compared. In all five, definite and in some cases remarkable improvement of the lesions was seen when 1,25-dihydroxyvitamin D3 at concentration of 0.5 microgram per g base was applied for two to five weeks. No local or systemic toxicity was detected in any patient. Although the mechanism of the improvement is yet to be elucidated, these results show the possible effectiveness of topical 1,25-dihydroxyvitamin D3 on psoriatic skin lesions.

Administration, Topical↗
PubMed1986

Serum vitamin D metabolites are not related to growth rate, bone mineral content, or serum alkaline phosphatase in male puberty.

Twenty boys were followed during their puberty for about 2 years with examinations every third month. At each examination we determined serum concentrations of 25OHD3, 1,25(OH)2D3, 24,25(OH)2D3, 25.26(OH)2D3, alkaline phosphatase (AP) and testosterone together with bone mineral content (BMC) at the distal forearm. Highly significant increases in both BMC (P less than 0.001), serum AP (P less than 0.001), and peak height velocity (PHV) followed the increase in serum testosterone. The boys were grouped according to time of maximal increase in BMC, AP, and PHV. The serum levels of the vitamin D metabolites were related to these points. No significant changes in any of the serum vitamin D metabolites were found. Thus vitamin D metabolism does not seem to be significantly influenced during the period of life when both the linear growth and bone mineralization is maximal.

24,25-Dihydroxyvitamin D 3↗
PubMed1985

Acute metabolic acidosis stimulates 3H-25 hydroxyvitamin D production by the rachitic rat liver.

Acute metabolic acidosis alters 1,25 dihydroxyvitamin D metabolism in experimental animals. We have used the NH4Cl-treated rachitic rat as a model to investigate the effect of acidosis on hepatic 25 hydroxyvitamin D (25 OHD) production. NH4Cl ingestion for 4 days was associated with a significant decrease in blood pH (7.44 +/- 0.03 vs 7.17 +/- 0.03, P less than 0.001) and bicarbonate (22.2 +/- 0.9 vs 10.5 +/- 1.6 mEq/liter, P less than 0.001). Acute metabolic acidosis stimulated 3H-25 hydroxyvitamin D production in liver homogenates. Acidosis resulted in a 52% decrease in Km (50.9 nM vs 24.5 nM) and an 11% decrease in the Vmax (554 picomoles/g liver protein/3 h vs 491 picomoles/g liver protein/3 h). The data collectively suggest that an acid load in vivo increases hepatic 25 OHD production and apparently enhances enzyme affinity for substrate.

Acidosis↗
PubMed1985

Changes in vitamin D metabolites and bone histology in rats during recovery from rickets.

The relative roles of 25-hydroxyvitamin D (25-OHD), 1,25-dihydroxyvitamin D (1,25-(OH)2D) and 24,25-dihydroxyvitamin D (24,25-(OH)2D) in bone mineralization are largely unknown. Young vitamin D depleted rats were fed increasing amounts of vitamin D and grouped radiologically in accordance with the rat line test. They ranged from severely rachitic to normal. Radiology was correlated with serum levels of 25-OHD, 1,25-(OH)2D, 24,25-(OH)2D, ionized calcium, magnesium, and phosphate, with bone histology, and with the total mineral content of the animals. Serum 1,25-(OH)2D rose in a linear fashion to supranormal values during bone healing and correlated with the radiological degree of rickets. Serum 25-OHD was below detection limit in the most rachitic and low in the radiologically normal rats, whereas 24,25-(OH)2D was low in all groups. These two metabolites showed no correlation with the radiologic, histologic or biochemical parameters. In rachitic rats, 1,25-(OH)2D appears to play a major role in bone healing and possibly exerts a direct effect on bone cells. It cannot be ruled out, however, that the effect is mediated through a rise in serum levels of calcium and phosphorus, although signs of bone healing were seen in the presence of a subnormal calcium X phosphorus product. Initiation of mineralization can take place with unmeasurable 25-OHD, and 24,25-(OH)2D seems to be without importance.

Animals↗
PubMed1992

Preventive effect of beta-alanyl-L-histidinato zinc on bone metabolism in rats fed on low-calcium and vitamin D-deficient diets.

The effect of beta-alanyl-L-histidinato zinc (AHZ) on bone metabolism in the femoral diaphysis of rats fed on low-calcium and vitamin D-deficient diets was investigated. Rats were orally administered AHZ (10, 30, and 100 mg/kg per day) for 14 days and were killed on the 15th day. Feeding with low-calcium and vitamin D-deficient diets caused a significant decrease in serum 25-hydroxy-vitamin D3, calcium, and inorganic phosphorus concentrations. These decreases were not prevented by AHZ administration. Meanwhile, the femoral-diaphyseal calcium and phosphorus contents were significantly reduced by feeding with the deficient diets. Decrease in bone calcium content was significantly prevented by the doses of 30 and 100 mg AHZ/kg. Furthermore, the dose of 100 mg AHZ/kg produced a significant increase in bone deoxyribonucleic acid (DNA) content and alkaline phosphatase activity in rats fed on the deficient diets. Bone zinc content in the deficient rats was significantly increased by the doses of AHZ (30 and 100 mg/kg). The present results suggest that oral administration of AHZ has a preventive effect in the development of deteriorating bone metabolism in rats fed on low-calcium and vitamin D-deficient diets.

Administration, Oral↗
PubMed1988

Initiation and characterization of primary mouse kidney epithelial cultures.

Primary cultures of murine renal epithelial cells were established from a preparation of proximal tubule fragments. Confluent cultures exhibited multiple dome formation, indicating the presence of tight junctions and an intact transcellular transport process. Ultrastructural analysis revealed a monolayer of polarized cells, with a sparse but clearly defined microvillar surface facing the growth medium and a basolateral surface attached to the substratum. Cultures grown on collagen gels did not show domes. The epithelial monolayer exhibited several differentiated functions of the proximal tubule: a) parathyroid hormone (PTH)-stimulated cAMP synthesis; b) production of 24,25-dihydroxyvitamin D3 from 25-hydroxyvitamin D3; c) high alkaline phosphatase activity; and d) Na+-dependent transport of phosphate (Pi) and alpha-methylglucoside (alpha-MG). The sugar uptake was selectively inhibited by phlorizin, a competitive inhibitor of glucose uptake at the luminal membrane. Kinetic analysis revealed independent transport systems for Pi and alpha-MG, with Km values corresponding to the high affinity systems identified in brush border membrane vesicles derived from the proximal tubule. Pi uptake by the epithelial monolayers was regulated by the concentration of Pi in the growth medium. Phorbol esters and PTH did not exert an effect on Pi and alpha-MG transport in mouse primary cultures. The present study demonstrates that primary cultures provide a useful in vitro preparation to investigate renal proximal tubular function.

24,25-Dihydroxyvitamin D 3↗
PubMed2004

Effects of 24,25(OH)2D3, 1,25(OH)2D3 and 25(OH)D3 on alkaline and tartrate-resistant acid phosphatase activities in fetal rat calvaria.

The aim of this work was to evaluate the effects of 24,25-dihydroxyvitamin D3, 24,25(OH)2D3, on alkaline phosphatase (AP) and tartrate-resistant acid phosphatase (TRAP) activities in fetal rat calvaria cultures. These actions were compared with those of 1,25-dihydroxyvitamin D3, 1,25(OH)2D3, and 25-hydroxyvitamin D3, 25(OH)D3, in similar experimental conditions. At 10 min, 30 min and at 24 h incubation time, 1,25(OH)2D3 (10(-10)M) and 25(OH)D3 (10(-7) M) produced a significant increase in AP and TRAP activities compared to control group (without vitamin D metabolites). However, 24,25(OH)2D3 (10(-7) M) only produced effects on phosphatase activities similar to those produced by 1,25(OH)2D3 and 25(OH)D3, after 24 h incubation time. These findings suggest that 1,25(OH)2D3 and 25(OH)2D3 could carry out actions in minutes (nongenomic mechanism), while 24,25(OH)2D3 needs longer periods of time to perform its biological actions (genomic mechanism).

24,25-Dihydroxyvitamin D 3↗
PubMed2003

Mitochondrial alkaline phosphatase as an intracellular signal in the synthesis of 1,25(OH)2D3 and 24,25(OH)2D3 in LLC-PK1 cells.

In previous works we have found a mitochondrial alkaline phosphatase (AP) activity in LLC-PK1. The aim of this work has been to study the possible involvement of mitochondrial AP activity in the synthesis of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) and 24,25-dihydroxyvitamin D3 (24,25(OH)2D3) from the substrate 25(OH)D3. Renal phenotype LLC-PK1 cells were incubated with 25(OH)D3 as substrate and treated with or without 1,25(OH)2D3, forskolin, 12-myristate-13-acetate (PMA) and 1,25(OH)2D3 in conjunction with PMA. Incubation of LLC-PK1 cells with forskolin (adenylate cyclase activator) not only stimulated the 1-hydroxylase and inhibited the 24-hydroxylase activities but also increased the mitochondrial AP activity. The addition of 1,25(OH)2D3, the main activator of 24-hydroxylase, produced a decrease of mitochondrial AP activity, a decrease of 1,25(OH)2D3 synthesis and an increase of the 24,25(OH)2D3 synthesis. Incubation with PMA, a potent activator of protein kinase C, did not produce any changes in mitochondrial AP activity, but an inhibition of 1,25(OH)2D3 and an activation of 24,25(OH)2D3 synthesis were found. Moreover, incubation of LLC-PK1 cells with PMA in conjunction with 1,25(OH)2D3 produced an additive effect in the decrease of 1,25(OH)2D3 and an increase of 24,25(OH)2D3 synthesis remaining mitochondrial AP activity as cells treated only with 1,25(OH)2D3. Our results suggest that mitochondrial AP activity could be involved as an intracellular signal in the regulation of 25(OH)D3 metabolism to the synthesis of 1,25(OH)2D3 and 24,25(OH)2D3 in renal phenotype LLC-PK1 cells through cAMP protein kinase system.

24,25-Dihydroxyvitamin D 3↗