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Biomedical subjects

H F DeLuca

Publications and source records attributed to H F DeLuca.

At least 559 records · Page 31Linked to original sources
PubMed1976

Control of renal vitamin D hydroxylases in birds by sex hormones.

Kidney homogenates from adult male Japanese quail or chickens demonstrate hydroxylase activity predominantly for the 24 rather than the 1 position of 25-hydroxyvitamin D3 (25-hydroxycholecalciferol). A single injection of 5 mg of estradiol-17beta into a male bird completely suppresses the 24-hydroxylase and greatly increases the 1-hydroxylase activity. Immature males do not respond well to estrogen alone, but they do respond well to estradiol plus testosterone. Testosterone alone has little or no effect on the hydroxylases of either species. Castrated male chickens show an estradiol response only when testosterone is also given. Optimal 24 hr responses to 5 mg of estradiol per kg in the castrate male were obtained with about 12 mg of testosterone per kg. These optimal amounts of estradiol and testosterone increased the activity of 25-hydroxyvitamin D3-1-hydroxylase approximately 225-fold (this enzyme is also known as 25-hydroxycholecalciferol 1-monooxygenase; 25-hydroxycholecalciferol, NADPH: oxygen oxidoreductase (hydroxylating), EC 1.14.13.13). These results demonstrate a strong regulation by the sex hormones of the renal vitamin D hydroxylases in birds.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗
PubMed1976

Metabolism of vitamin D: current status.

There has been much progress in our understanding of the metabolism of vitamin D. It is now clear that vitamin D3 can be produced in the skin or ingested in the diet. It accumulates very rapidly in the liver where it undergoes 25-hydroxylation, yielding 25-OH-D3, the major circulating metabolite of the vitamin. 25-OH-D3 proceeds to the kidney where it undergoes one of two hydroxylations. If there is a biological need for calcium or for phosphate the kidney is stimulated to convert 25-OH-D3 to the 1,25-(OH)2-D3, a calcium and phosphate mobilizing hormone. If, however, the animal has sufficient supplies of calcium and phosphate, the l-hydroxylase is shut down and instead the 25-OH-D3 is converted to a 24,25-(OH)2D3. The role of the 24,25-(OH)2D3 remains unknown; it may be an intermediate in the inactivation-excretion mechanism. 1,25-(OH)2D3 proceeds to the intestine where it stimulates intestinal calcium transport and intestinal phosphate transport. It also stimulates bone calcium mobilization and probably has other effects yet to be discovered in such tissues as muscle. The 25-OH-D3-l-hydroxylase, which is located exclusively in renal mitochondria, has been shown to be a three component system involving a flavoprotein, an iron-sulfur protein (renal ferredoxin), and a cytochrome P-450. This system has been successfully solubilized, the components isolated, and reconstituted. The 24-hydroxylase, however, has not yet been thoroughly studied. 1,25-(OH)2D3 is necessary for the appearance of the 24-hydroxylase; parathyroid hormone represses 24-hydroxylation. It is possible that the 24-hydroxylase represents the major regulated enzyme, so that its presence or absence may determine whether 1,25-(OH)2D3 is produced. Two metabolic pathways for 1,25-(OH)2D3 are known, conversion by the 24-hydroxylase to 1,24,25-(OH)3D3, and conversion of 1,25-(OH)2D3 to an unknown substance. In the latter instance, there occurs loss of a side chain piece, including at least one of the 26 and 27 carbons. Whether 1,25-(OH)2D3 must be metabolized further before it carries out all of its functions has yet to be established. The primary excretion route of vitamin D3 is via the bile into the feces. Urinary excretion appears small in magnitude and no excretion products have yet been identified positively. Much remains to be learned concerning the metabolism and function of vitamin D and its metabolites. This should therefore, prove to be a fruitful area of investigation for many years to come, especially since 1,25-(OH)2D3, 25-OH-D3, and lalpha-OH-D3 have been shown to be effective in a number of metabolic bone disease states.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗
PubMed1976

Jejunal and ileal absorption in patients with chronic renal disease. Effect of 1alpha-hydroxycholecalciferol.

Calcium absorption in 30-cm segments of small intestine was measured by constant perfusion of test solutions containing different concentrations of calcium gluconate. In both the jejunum and ileum, calcium absorption rates increased progressively as luminal calcium concentration was increased stepwise between 1 and 20 mM. Although calcium transport was not saturable within these limits, unidirectional flux ratios of calcium (47Ca) suggest that calcium absorption is active in both the jejunum and ileum. Calcium absorption in patients with chronic renal disease was markedly depressed in both regions of the small intestine. This was due to decreased flux out of the lumen; flux in the reverse direction was normal. Flux ratios in the renal disease patients showed no evidence for active calcium transport. Treatment of these patients for 1 wk within 2 mug/day of 1alpha-hydroxycholecalciferol [1alpha-(OH)-D3] restored net calcium absorption and unidirectional calcium flux out of the lumen to normal values in the jejunum; in the ileum, 1alpha-(OH)-D3 increased calcium absorption 60-83% of normal at the various luminal calcium concentrations. 1alpha(OH)-D3 had no effect on unidirectional calcium flux into the lumen or on xylose and electrolyte absorption in either area of the small intestine.

Biological Transport↗
PubMed1976

Influence of dietary phosphorus on renal phosphate reabsorption in the parathyroidectomized rat.

Inorganic phosphate (Pi) reabsorption was studied during Pi infusion, after acute or chronic thyroparathyroidectomy (TPTX), in rats stabilized on a high-phosphorus (1% P) or a low-phosphorus (0.02% P) diet. After acute TPTX, there were no consistent differences in Pi reabsorption between the high- and low-phosphorus dietary groups. After chronic TPTX, the rats stabilized on the low-phosphorus diet exhibited nearly complete Pi reabsorption at every plasma Pi level, while the animals receiving the high-phosphorus diet manifested a marked phosphaturic response to Pi infusion. In addition, Pi reabsorption was significantly increased in the chronic TPTX low-phosphorus rats which achieved the highest filtered Pi loads, while their urine remained essentially phosphate-free. Dietary phosphorus-dependent alterations in Pi reabsorption may play a significant role in establishing the rate of Pi excretion per nephron under certain circumstances and should be considered in the interpretation of studies investigating renal Pi handling. The ability of phosphorus-depleted animals to maintain a phosphate-free urine during Pi loading would favor the rapid repletion of body phosphorus stores.

Absorption↗
PubMed1976

The effect of hepatectomy on the synthesis of 25-hydroxyvitamin D3.

The metabolism of [3H]vitamin D3 in hepatectomized vitamin D-deficient rats has been studied. Hepatectomy drastically disrupts vitamin D3 metabolism as revealed by prolonged high levels of [3H] vitamin D3 in the plasma compartment even 12 h after dose in contrast to sham-operated controls. Some conversion of [3H] vitamin D3 to [3H]25-hydroxyvitamin D3 was detected in hepatectomized rats, but the amount was small in spite of the high circulating levels of [3H]vitamin D3. Since the liver initially takes up much of an administered dose in normal animals and the conversion of [3H]vitamin D3 to [3H]25-hydroxyvitamin D3 is small in hepatectomized rats in spite of high circulating [3H]-vitamin D3, it is concluded that the liver plays a major role in the metabolism of vitamin D3 to 25-hydroxy-vitamin D3.

Animals↗
PubMed1976

Bone demineralization in renal failure: a longitudinal study of the distal femur using photon absorptiometry.

The bone mineral content (BMC) of the lower end of the femur was measured by photon absorptiometry in 87 patients with chronic renal failure. The gamma-ray photon source was Am241. Serial measurements were obtained for up to two years. The mean BMC of the adult patients, comprising: 18 pre-dialysis (CRF), 41 chronic haemodialysis (CHD) and 19 renal transplant (RT) patients were all significantly lower than controls with the exception of the male CRF group. Two adults and one child on chronic haemodialysis showed a significant rate of bone loss (less than 2% per year). In one of these adults the addition of daily oral 1 alpha hydroxycholecalciferol was associated with no further reduction in BMC. Two children and one adult on chronic haemodialysis showed a significant rate of increase in BMC (less than 2% per year). This adult had had a tendency to loss of BMC on standard CHD treatment but after receiving parenteral 1,25 dihydroxycholecalciferol three times weekly showed a significant rate of loss of BMC on serial measurement. Two adults and one child with CRF had a significant rate of increase in BMC on standard treatment.

Adolescent↗
PubMed1976

Vitamin D endocrinology.

Current status of our understanding of the metabolism of vitamin D and its implications in metabolic bone disease is reviewed. The details of metabolism of vitamin D3 to 25-hydroxyvitamin D3 in the liver and its further conversion in the kidneys to either 1,25-dihydroxyvitamin D3 or 24,25-dihydroxyvitamin D3 are presented. The latter conversions are regulated by the vitamin D status, serum calcium through the parathyroid gland system, and serum inorganic phosphorus concentration. The 1,25-dihydroxyvitamin D3 can now be regarded as a calcium- and a phosphate-mobilizing hormone and must be considered as one of the most important serum calcium-regulating hormones. Disruption of the vitamin D metabolic sequence or the signal system for 1,25-dihydroxyvitamin D3 results in several bone and calcium metabolism disorders such as renal osteodystrophy, hypoparathyroidism, pseudohypoparathyroidism, and vitamin D-dependency rickets. The use of the synthetic analogs of 1,25-dihydroxyvitamin D3 as well as 1,25-dihydroxyvitamin D3 itself in the management of these disease states is discussed.

Animals↗
PubMed1976

1 alpha-hydroxycholecalciferol in hemodialysis renal osteodystrophy. Adverse effects of anticonvulsant therapy.

Two regular hemodialysis patients were assessed before, during and after therapy for 8 1/2 months with 1alpha-hydroxycholecalciferol (1alphaOHD3). The first patient (F.S.), treated with 2 mug daily, improved considerably with complete resolution of histological osteomalacia (O.M.), reduction in osteitis fibrosa (O.F.) and healing of Looser zones. The second patient (T.Y.), who was treated at the same time with a combination of phenobarbitone and phenytoin, showed no improvement while taking 3 mug of 1alphaOHD3 daily. It is suggested that hepatic microsomal enzyme inducing drugs antagonize the action of 1alphaOHD3 by interfering with its subsequent hepatic 25-hydroxylation.

Alkaline Phosphatase↗
PubMed1975

Synthesis of (6-3H)-1alpha-hydroxyvitamin D3 and its metabolism in vivo to (3H)-1alpha,25-dihydroxyvitamin D3.

[6-3H]-1alpha-Hydroxyvitamin D3 was chemically synthesized and its full biological activity and radiochemical purity were demonstrated. With the use of this preparation it has been possible to demonstrate in vivo that in rats the [6-3H]-1Alpha-hydroxyvitamin D3 is converted to [6-3H]-1alpha,25-dihydroxyvitamin D3, the natural hormone. In fact, in the intestine and bone of rats given 32 picomoles of [6-3H]-1alpha-hydroxyvitamin D3 each day for 6 days, more than 80 percent of the lipid-soluble radioactivity exists as [6-3H]-1alpha,25-dihydroxyvitamin D3, a finding that suggests that much of the biological effectiveness of 1alpha-hydroxyvitamin D3 is due to its conversion to 1alpha,25-dihydroxyvitamin D3.

Animals↗
PubMed1975

Treatment of hypoparathyroidism and pseudohypoparathyroidism with metabolites of vitamin D: evidence for impaired conversion of 25-hydroxyvitamin D to 1 alpha,25-dihydroxyvitamin D.

In hypoparathyroidism and pseudohypoparathyroidism, pharmacologic doses of vitamin D correct hypocalcemia, but the mechanism is unknown. In two children with hypoparathyroidism and one with pseudohypoparathyroidism we tested the hypothesis that in these conditions there is a defect in synthesis of 1 alpha,25-dihydroxyvitamin D3, the principal active metabolite of vitamin D. In both conditions, minute doses of the metabolite (0.04 to 0.08 mug per kilogram of body weight per day) quickly corrected hypocalcemia and increased intestinal calcium absorption. On the other hand, the effective dose of 25-hydroxyvitamin D3 to maintain normocalcemia was 3 to 4 mug per kilogram per day in the two conditions. Thus, the dosage ratio of 25-hydroxyvitamin D3 to 1 alpha,25-dihydroxyvitamin D3 approximated 100:1. By contrast this ratio was approximately 3:1 in two infants with vitamin D deficiency, a condition in which optimal metabolism of vitamin D would be expected. These findings suggest an impaired conversion of 25-hydroxyvitamin D to 1 alpha,25-dihydroxyvitamin D in both hypoparathyroidism and pseudohypoparathyroidism.

Administration, Oral↗
PubMed1975

1-alpha-hydroxyvitamin D3 in chronic renal failure. A potent analogue of the kidney hormone, 1,25-dihydroxycholecalciferol.

In chronic renal disease, the synthesis of the kidney hormone, 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3), is impaired, thus contributing to the development of renal osteodystrophy. The clinical use of 1,25-(OH)2D3 is limited, due to the complexity and expense of its chemical synthesis. This study reports the use of 1-alpha-hydroxyvitamin D3 (1-alpha-OH-D3), an active analogue of 1,25-(OH)2D3, in eight patients with chronic renal failure, five of whom were undergoing long-term hemodialysis. The drug was given orally for 6 to 260 days at a dosage of 1mug to 4mug/day. Short-term (21 days) balance studies showed an increase in intestinal calcium absorption and a simultaneous fall in serum parathyroid hormone levels during administration of 1-alpha-OH-D3. In two long-term studies (160 and 260 days), roentgenographic improvement of renal osteodystrophy was seen after 45 and 185 days, respectively. The data indicate that 1-alpha-OH-D3 holds considerable promise for the prevention and treatment of renal osteodystrophy.

Administration, Oral↗