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H F DeLuca

Publications and source records attributed to H F DeLuca.

At least 415 records · Page 23Linked to original sources
PubMed1980

Characterization of a receptor-like protein for 1,25-dihydroxyvitamin D3 in rat skin.

Isolated rat epidermis possesses a cytosolic 3.5 S receptor-like protein for 1,25-dihydroxyvitamin D3. This 3.5S binder has a high affinity (Kd = 1.4 X 10(-10) M) for 1,25-dihydroxyvitamin D3 and is present in low concentrations (31 fmol of binding sites per mg of cytosol protein). Analog competition for receptor binding revealed the following potency order: 1,25-dihydroxyvitamin D3 > 25-hydroxyvitamin D3 > 1 alpha-hydroxyvitamin D3 > 24 (R),25-dihydroxyvitamin D3 > vitamin D3. The receptor has a molecular weight of 60,000, has affinity for DNA-cellulose, and aggregates in the presence of low potassium concentrations. The 1,25-dihydroxyvitamin D3 binder is stabilized by sodium molybdate (10 mM). Addition of phenylmethylsulfonyl fluoride (3 mM) was found to yield more reproducible receptor preparations. The presence of a 1,25-dihydroxyvitamin D3 binding macromolecule with properties similar to those of the bone and intestinal receptor suggests that skin is an additional target organ for this hormone.

Animals↗
PubMed1980

Role of kidney tissue in the production of 25-hydroxyvitamin D3-26,23-lactone and 1 alpha, 25-dihydroxyvitamin D3-26,23-lactone.

Labeled 25-hydroxyvitamin D3-26,23-lactone was isolated from the serum of vitamin D-repleted rats given [3 alpha-3H]-25-hydroxyvitamin D324 hr prior to sacrifice. The metabolite was identified by cochromatography with the authentic lactone on straight-phase and reversed-phase high-performance liquid chromatography. Production of the lactone was abolished by nephrectomy indicating that the kidney is the site of synthesis. Homogenate of kidneys from chickens given large doses of vitamin D can carry out in vitro production of the lactone from 25-hydroxyvitamin D3. When 1 alpha, 25-dihydroxyvitamin D3 was used as substrate, this system produced only traces of a compound believed to be 1 alpha, 25-dihydroxyvitamin D3-26,23-lactone. However, incubation of rachitic chicken kidney homogenates with 25-hydroxyvitamin D3-26,23-lactone produced substantial amounts of a compound that has been identified by mass spectrometry as 1 alpha, 25-dihydroxyvitamin D3-26,23-lactone. Thus, the development of a functional group on C-26 and eventual lactone formation takes place in kidney by a system acting on 25-hydroxyvitamin D3.

Animals↗
PubMed1980

Cellular and subcellular localization of 1,25-(OH)2-vitamin D3 in rat kidney: comparison with localization of parathyroid hormone and estradiol.

Results of thaw-mount autoradiographic studies of kidney obtained 1--3 hr after a single injection of 1,25-(OH)2-[3H]vitamin D3 to rats showed strong nuclear concentration of radioactivity in podocytes and cells of distal tubules, including the pars convoluta, macula densa, and pars recta. Intermediate nuclear concentration was found in cells of the thin limb of Henle's loops, whereas weak or no nuclear uptake was seen in cells of the proximal tubules. In contrast, after injection of 3H-labeled parathyroid hormone or [3H]estradiol, mainly cells of the proximal tubules were labeled; after 3H-labeled parathyroid hormone, apical cytoplasmic uptake of radioactivity was seen most strongly in the proximal part of the proximal tubules, whereas, after [3H]estradiol, weak nuclear concentration was seen in cells throughout the proximal tubules. The results are consistent with the concept that synthesis of 1,25-(OH)2-vitamin D3 occurs in the proximal tubules under stimulation of parathyroid hormone or estradiol (or other hormones) and that the major site of action of 1,25-(OH)2-vitamin D3 is in the distal tubules.

Animals↗
PubMed1980

Characterization of retinoyl beta-glucuronide as a minor metabolite of retinoic acid in bile.

Several metabolites detected in the bile of rats given radioactive retinoic acid were separated by liquid/gel partition chromatography and purified by high-pressure liquid chromatography. One of these metabolites was found to be sensitive to beta-D-glucuronidase, yielding both 13-cis- and all-trans-retinoic acid. It had the characteristic ultraviolet absorption spectrum of retinoic acid esters. Trimethylsilyl ether and acetyl derivatives of the methylated metabolite were prepared and examined by mass spectrometry. The resulting mass spectra established the structure to be retinoyl beta-glucuronide. Retinoyl glucuronide was rapidly excreted into the bile: the excretion was complete by 12 hr after the administration of retinoic acid. At this time the metabolite represented 12% of bile radioactivity (10% of dose). These observations confirm the existence of retinoyl glucuronide but demonstrate that it represents only one of several retinoic acid metabolites in bile.

Animals↗
PubMed1980

The vitamin d hormonal system: implications for bone diseases.

A half century ago, vitamin D was recognized as a vitamin. Now it has become clear that it is also a hormone--indeed the biochemical cornerstone of a major hormonal system involved in regulating the body's calcium economy. The active metabolite, calcitriol, produced in the kidney, acts on bone and intestine and has been found effective in therapy of osteodystrophy and perhaps other metabolic bone diseases.

Calcium↗
PubMed1980

The effect of dietary protein on the biological activity of cholecalciferol and its metabolites in the rachitic rat.

Rats maintained on low-protein rachitogenic diets show increased intestinal calcium transport, serum inorganic phosphate and increased endochondral calcification responses to calciferol, 25-hydroxycholecalciferol (25-OH-CC) and 1,25-dihydroxycholecalciferol (1,25-(OH)2CC). Because enhanced responses are observed with 1,25-dihydroxycholecalciferol as well as its precursors, it is unlikely that the effect of dietary protein is mediated by a change in the calciferol-25-hydroxylase and the 25-hydroxycholecalciferol-1 alpha-hydroxylase. Instead, it appears that either metabolism of 1,25-dihydroxycholecalciferol or its activity in the target organs is affected.

Animals↗
PubMed1980

Effect of vitamin D deficiency on fertility and reproductive capacity in the female rat.

The effects of vitamin D deficiency on fertility, reproductive capacity and on fetal and neonatal development were investigated. Female weanling rats were maintained on either a vitamin D-replete or vitamin D-deficient diet until maturity and mated with normal males. Vitamin D-deficient females were capable of reproduction. However, vitamin D deficiency reduced overall fertility by 75%, diminished litter sizes by 30% and impaired neonatal growth from day 6 to day 15 of lactation. Fetal development asjudged by weight gain and viability appeared normal. Neonatal viability was also normal even though growth was retarded. The concentrations of calcium and inorganic phosphate in milk from vitamin D-replete and vitamin D-deficient mothers were similar implying that the transfer of calcium and phosphorus from the plasma to the milk is a vitamin D-independent process.

Animals↗
PubMed1980

The control of calcium and phosphorus metabolism by the vitamin D endocrine system.

Vitamin D, which is normally produced in the skin under ultraviolet irradiation, is the building block for a new endocrine system that involves hydroxylation on the 25-position in the liver followed by 1 alpha-hydroxylation in the kidney to produce the vitamin D hormone, 1 alpha, 25-(OH)2D3. This vitamin D hormone functions in the intestine, bone, and kidney to stimulate transport of calcium and phosphorus into the extracellular fluid compartment upon demand. The production of the vitamin D hormone is tightly feedback regulated directly or indirectly by calcium and phosphorus levels of the plasma. The vitamin D endocrine system is an important one in the regulation of calcium and phosphorus metabolism but is not solely responsible for the calcium and phosphorus transfer reactions occurring during reproduction. The vitamin D hormone functions in the target organs by a nuclear-mediated receptor-based mechanism probably involving the biogenesis of calcium and phosphorus transfer proteins. New target sites of 1,25-(OH)2D3 action in several tissues are suggested by this nuclear localization in those cells. Study of the vitamin D endocrine system has provided a new understanding of metabolic bone diseases and has provided new forms of vitamin D for their treatment. Thus a basic investigation of the regulation of calcium and phosphorus metabolism has rewarded medicine and science with new therapeutic approaches to disease problems.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗
PubMed1980

Calcium transport in small intestine during pregnancy and lactation.

The factors involved in calcium homeostasis during the mammalian reproductive cycle and specifically in the control of active calcium transport in the intestine have not been thoroughly investigated. For this reason calcium transport in the intestine was measured in vitamin D-replete and vitamin D-deficient rats during pregnancy and lactation using the everted gut sac technique. In addition the changes in the plasma concentrations of calcium and 1,25-dihydroxyvitamin D were measured and correlated with transport. During the later stages of pregnancy and during lactation, the concentration of calcium in the plasma is reduced 10-30%. In turn, in the vitamin D-replete rat, the concentration of 1,25-dihydroxyvitamin D in the plasma increases from a control value of 26 pg/ml to 158 pg/ml at day 14 of lactation. Calcium transport in the intestine increases late in pregnancy, peaks during lactation, and then falls to control values by 3 wk postweaning in both vitamin D-replete and D-deficient animals. These findings strengthen the established relationship between 1,25-dihydroxyvitamin D and active calcium transport in the intestine as well as suggest that some factor(s) independent of vitamin D is stimulating intestinal calcium transport during the reproductive cycle.

Animals↗
PubMed1980

Calcium transport in small intestine during early development: role of vitamin D.

To define the role of vitamin D in calcium transport in the intestine during early development, female weanling rats were placed on vitamin D-replete or vitamin D-deficient diets, grown to maturity, and mated with normal males. Pups born to vitamin D-replete and vitamin D-deficient mothers were killed at various times after parturition, and calcium transport in the small intestine as well as the concentrations of calcium and phosphate in the plasma were measured. Transport of calcium in pups from vitamin D-replete and vitamin D-deficient litters was identical at 3 and 14 days postpartum but was threefold greater in pups from vitamin D-replete litters at weaning and 3 wk postweaning. 1,25-dihydroxyvitamin D3 had no effect on calcium transport at 14 days postpartum but did induce transport at weaning. Plasma concentrations of calcium at 3 days postpartum were nearly normal but decreased during the suckling period from 10.3 mg/100ml to 7.2 mg/100 ml in vitamin D-deficient rats. These results suggest that calcium transport in the intestine during early development is not mediated by vitamin D but that a vitamin D-sensitive transport system develops late in the suckling period.

Age Factors↗