Search PubMed⌕ Search

Biomedical subjects

H F DeLuca

Publications and source records attributed to H F DeLuca.

At least 181 records · Page 10Linked to original sources
PubMed1989

Vitamin D is necessary for reproductive functions of the male rat.

The effect of vitamin D deficiency on the fertility and reproductive capacity of male rats was investigated. Male weanling rats were fed vitamin D-deficient or vitamin D-replete diets until maturity, and mated to age-matched, vitamin D-replete females. Vitamin D-deficient males were capable of reproduction. However, successful matings, i.e., presence of sperm in the vaginal tract of the female, by vitamin D-deficient males were reduced by 45% when compared to matings by vitamin D-replete males. Fertility (successful pregnancies in sperm-positive females) was reduced by 73% in litters from vitamin D-deficient male inseminations when compared to litters from females inseminated by vitamin D-replete males. These results demonstrate that vitamin D and its metabolites are necessary for normal reproductive functions in the male rat.

Animals↗
PubMed1989

1,25-Dihydroxyvitamin D3 restores fertility of vitamin D-deficient female rats.

Vitamin D deficiency reduces mating success and fertility in female rats, but it is not known if the reduction in reproductive performance is a direct action of vitamin D or the hypocalcemia associated with vitamin D deficiency. The effect of vitamin D deficiency with normocalcemia on fertility and reproductive capacity in female rats was investigated. Female weanling rats were maintained on vitamin D-deficient or vitamin D-replete diets until maturity and mated to age-matched, normal, vitamin D-replete males. Three groups of vitamin D-deficient females were maintained on diets varying in calcium and Pi concentrations to test the effect of vitamin D deficiency with different serum calcium and Pi concentrations on reproductive performance. Vitamin D-deficient females were capable of reproduction, but successful matings by all groups of vitamin D-deficient females were markedly reduced regardless of serum calcium concentration, when compared with matings with vitamin D-replete females. Fertility was also drastically reduced in litters from all groups of vitamin D-deficient females regardless of serum calcium concentration, when compared with litters from vitamin D-replete females. Vitamin D-deficient female rats that received vitamin D or 1,25-dihydroxyvitamin D3 were capable of successfully mating and giving rise to normal, healthy litters. These results indicate that vitamin D and not hypocalcemia is directly responsible for reduced reproductive capacity and fertility in vitamin D-deficient female rats.

Animals↗
PubMed1988

Purification and properties of an 18-kilodalton, 1,25-dihydroxyvitamin D3 modulated protein from embryonic chick intestine.

An 18,000-dalton protein (pI = 5.1) shown previously to be modulated by 1,25-dihydroxyvitamin D3 was purified to allow its further characterization. This protein from embryonic chick intestine was shown to comigrate during two-dimensional electrophoresis with an abundant protein from the intestine of 4-week-old chickens. The protein was purified from 4-week chick intestine and analyzed for amino acid composition, and 28 amino acids of its N-terminal sequence were determined. The N-terminal amino acid sequence had significant homology to cellular retinol binding protein II, an intestinal protein that has been recently sequenced. The purified 18-kilodalton protein was shown to bind retinol by fluorescence spectrophotometry. This 18-kilodalton protein is dramatically changed by 1,25-dihydroxyvitamin D3 in the chick embryonic organ culture system. Therefore, further study of it may lead to a better understanding of vitamin A and D interaction and how 1,25-dihydroxyvitamin D3 acts through proteins to stimulate intestinal calcium and phosphate transport.

Amino Acid Sequence↗
PubMed1988

The plasma binding protein for vitamin D is a site of discrimination against vitamin D-2 compounds by the chick.

The binding of 25-hydroxy-[26,27-3H]vitamin D-3 and 25-hydroxy-[26,27-3H]vitamin D-2 to the vitamin D binding protein in the plasma of both rats and chicks has been studied. In the case of rats, sucrose density gradient analysis, competitive displacement, and Scatchard analysis demonstrate that 25-hydroxyvitamin D-3 and 25-hydroxyvitamin D-2 are bound equally well to the vitamin D binding protein. In contrast, 25-hydroxyvitamin D-2 is poorly bound, while 25-hydroxyvitamin D-3 is tightly bound to the vitamin D binding protein in chick plasma. On the other hand, the chick intestinal receptor binds 1,25-dihydroxyvitamin D-2 and 1,25-dihydroxyvitamin D-3 equally well with a KD of 7.10(-11) M for both compounds. These results strongly suggest that the failure of the plasma transport protein in chicks to bind the vitamin D-2 compounds may be responsible for their relative ineffectiveness in these animals.

25-Hydroxyvitamin D 2↗
PubMed1988

The vitamin D story: a collaborative effort of basic science and clinical medicine.

The discovery in 1919-1924 of vitamin D and its production in skin and foods by UV irradiation led to the elimination of rickets as a major medical problem. The identification and chemical preparation of vitamin D in the next decade provided large quantities of vitamin D to the physician for the treatment of a variety of metabolic bone diseases. Early in the 1960s, little was known about the function of vitamin D in causing mineralization of the skeleton, and hence in preventing the disease rickets in children and osteomalacia in adults. With the application of modern tools of biochemistry came the discovery that vitamin D must first be modified by 25-hydroxylation in the liver followed by 1 alpha-hydroxylation in the kidney to produce the vitamin D hormone 1 alpha,25-dihydroxyvitamin D3 [1,25-(OH)2D3]. This process is strongly feedback-regulated and is one of the major endocrine systems regulating plasma calcium and phosphorus concentrations. Furthermore, it is a major endocrine system regulating bone mass and state. With the chemical synthesis of 1,25-(OH)2D3 and many of its analogs has come the possibility of treating a number of metabolic bone diseases not previously managed adequately, such as vitamin D-resistant rickets, hypoparathyroidism, renal osteodystrophy, and osteoporosis. By using 1,25-(OH)2D3, considerable work has been carried out to understand how this hormone facilitates calcium transport across the intestinal membrane. Modern work is described on the molecular mechanism of action of the vitamin D hormone in eliciting the cellular responses that result in mineral homeostasis. The possible use of the vitamin D analogs to bring about differentiation of myelocytic-type leukemias and in the treatment of psoriasis has been an important new development. This paper will thus be a blend of basic science of the vitamin D system and the application of that information to the treatment of disease.

Animals↗
PubMed1988

Long term follow-up of bone mineral status in children with renal disease.

Bone mineral content (BMC) was measured by photon absorptiometry in the non-dominant forearm of children with chronic renal failure followed for a total of 2472 months. From 48 children, 302 measurements were made, and changes which occurred in BMC over time were correlated with several factors. Patients were divided into those who had received glucocorticoids (group 1) and those who had not (group 2). Group 1 patients had a lower mean serum creatinine (Cr) (p less than 0.05), a lower growth velocity (p greater than 0.02) and were more demineralized than group 2 patients. There was no correlation between BMC and height velocity or estimated creatinine clearance. BMC and height Z-score (SDS) were highly correlated. Over the period of study, group 1 patients remained shorter, had a lower height velocity, a lower BMC Z-score and a lower BMC for each serum creatinine level. Long-term therapeutic intervention with oral 1,25(OH)2D improved bone mineral status in three children in the nonsteroid group, but none of those in the steroid group. This study demonstrates that steroid administration is probably the most important factor causing bone demineralization, possibly even more important than renal failure.

Adolescent↗
PubMed1988

Regulation of the intestinal 1,25-dihydroxyvitamin D3 receptor during neonatal development in the rat.

Monoclonal antibodies have been used to examine the regulation of expression of the rat intestinal receptor for 1,25-dihydroxyvitamin D3 during neonatal development. 1,25-Dihydroxyvitamin D3 binding activity increases dramatically between Days 15 and 28 postpartum in normal neonatal rats. Immunoprecipitation and combined immunoprecipitation-immunoblotting experiments demonstrate that this increase in hormone binding activity is caused by an increase in the amount of receptor protein present in rat intestine between Days 18 and 28 of age. Very little receptor protein, if any, appears to be present in rat intestine prior to Day 18 of life. These results suggest that the expression of the gene for 1,25-dihydroxyvitamin D3 receptor is regulated during neonatal development in the rat.

Animals↗
PubMed1988

Renal 25-hydroxyvitamin D3-1-hydroxylase in patients with renal disease.

Renal 25-hydroxyvitamin D3-1-hydroxylase (1-hydroxylase) activity has been measured in 20 patients with renal disease using the remaining portion of needle renal biopsy specimens taken for diagnostic purposes and in five patients using kidney tissue removed during transplantation. The 1-hydroxylase activity of 12 patients with asymptomatic proteinuria and/or hematuria (group A) measured 83.2 +/- 37.7 pg/mg tissue/20 min. Since these 12 patients did not show impaired mineral metabolism or pathological changes in the renal tubules, we have presumed that these results indicate normal activity in man. We also measured the 1-hydroxylase activity in four patients treated with prednisolone (group B). The 1-hydroxylase activity (81.1 +/- 27.1 pg/mg tissue/20 min) of group B did not differ from that of group A. However, the urinary excretion of calcium (ratio of calcium/creatinine) was increased (0.18 +/- 0.07 vs. 0.07 +/- 0.03, P less than 0.01) by prednisolone therapy. These data suggest that glucocorticoid-induced changes in urinary calcium excretion are not the result of a direct effect of glucocorticoid on renal 1-hydroxylase. In the three patients with mild renal insufficiency (group C), the 1-hydroxylase activity (75.4 +/- 22.4 pg/mg tissue/20 min) did not differ from that of group A. However, in five patients with severe renal insufficiency (group D), the 1-hydroxylase activity (8.5 +/- 3.7 pg/mg tissue/20 min) was significantly decreased (P less than 0.01).

25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗
PubMed1988

Structure and nucleotide sequence of the rat intestinal vitamin D-dependent calcium binding protein gene.

The vitamin D-dependent intestinal calcium binding protein (ICaBP, 9 kDa) is under transcriptional regulation by 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3], the hormonal active form of the vitamin. To study the mechanism of gene regulation by 1,25-(OH)2D3, we isolated the rat ICaBP gene by using a cDNA probe. Its nucleotide sequence revealed 3 exons separated by 2 introns within approximately 3 kilobases. The first exon represents only noncoding sequences, while the second and third encode the two calcium binding domains of the protein. The gene contains a 15-base-pair imperfect palindrome in the first intron that shows high homology to the estrogen-responsive element. This sequence may represent the vitamin D-responsive element involved in the regulation of the ICaBP gene. The second intron shows an 84-base-pair-long simple nucleotide repeat that implicates Z-DNA formation. Genomic Southern analysis shows that the rat gene is represented as a single copy.

Amino Acid Sequence↗
PubMed1988

Structure and regulation of the rat 1,25-dihydroxyvitamin D3 receptor.

Complementary DNA clones encoding the entire rat 1,25-dihydroxyvitamin D3 receptor were isolated, and the total 423-amino acid sequence was deduced. The amino acid sequence of the rat receptor is similar but not identical to the reported human receptor sequence. The cysteine-rich DNA-binding domain is completely conserved and the steroid-binding domain is greater than 93% conserved between rat and human. The cDNA was used as a probe in blot analysis of polyadenylylated RNA to show that the 1,25-dihydroxyvitamin D3 receptor mRNA is a single 4.4-kilobase mRNA that is expressed in intestine and kidney, slightly expressed in heart, and not detectable in liver and spleen. The receptor mRNA concentration is markedly increased during development of the rat intestine between day 14 and day 21, in accord with previous results obtained by measurement of receptor concentration by ligand binding or immunoblotting.

Amino Acid Sequence↗
PubMed1988

Isolation and expression of rat 1,25-dihydroxyvitamin D3 receptor cDNA.

The cDNA for the 1,25-dihydroxyvitamin D3 receptor has been isolated by screening a rat kidney lambda gt11 expression library with a mixture of three previously identified anti-receptor monoclonal antibodies. Protein produced from this cDNA reacts with each of the three monoclonal antibodies but does not react with an antibody specific for the porcine receptor or an irrelevant antibody. In addition, the expressed protein specifically binds 1,25-dihydroxyvitamin D3 but does not bind estradiol, progesterone, testosterone, cortisol, or aldosterone. The nucleotide sequence for this cDNA has been determined and used to deduce the amino acid sequence of the protein. This amino acid sequence contains a region that matches perfectly the partial amino acid sequence determined for the receptor isolated from porcine intestine. This amino acid sequence also closely matches the reported amino acid sequence of the putative DNA-binding finger of the avian 1,25-dihydroxyvitamin D3 receptor.

Amino Acid Sequence↗
PubMed1988

Partial amino acid sequence of porcine 1,25-dihydroxyvitamin D3 receptor isolated by immunoaffinity chromatography.

Monoclonal antibodies against the porcine 1,25-dihydroxyvitamin D3 receptor were immobilized on Sepharose CL-4B and used to obtain a highly purified 1,25-dihydroxyvitamin D3 receptor fraction with a 45% recovery of the 1,25-dihydroxyvitamin D3 binding capacity. The porcine receptor was purified to homogeneity by preparative electrophoresis and digested in sodium dodecyl sulfate/polyacrylamide gels with Staphylococcus aureus strain V8 protease. The resulting peptides were separated by sodium dodecyl sulfate/polyacrylamide gel electrophoresis, electrophoretically transferred to polyvinylidene difluoride membranes, and directly sequenced. The generation and isolation of peptides by this method allows sequencing of proteins present in trace amounts as well as those whose amino termini have been modified. The 1,25-dihydroxyvitamin D3 receptor amino acid sequence corresponded to the sequence predicted from a recently cloned receptor cDNA obtained from rat kidney mRNAs.

Amino Acid Sequence↗
PubMed1988

Biological activity of 1,25-dihydroxyvitamin D2 and 24-epi-1,25-dihydroxyvitamin D2.

The biological activity of 1,25-dihydroxyvitamin D2 [1,25(OH)2D2] and 24-epi-1,25-dihydroxyvitamin D2 [24-epi-1,25(OH)2D2] has been determined in vitamin D-deficient rats. The biological effectiveness of 1,25(OH)2D2 is equal to that reported previously for 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] (15) in intestinal calcium transport, mineralization of bone, mobilization of bone calcium, and elevation of plasma inorganic phosphorus of rachitic rats. However, 24-epi-1,25(OH)2D2 is at best one-half as active as 1,25(OH)2D2 in stimulating intestinal calcium transport and in the mineralization of rachitic bone. The 24-epi-1,25(OH)2D2 is one-third as active as 1,25(OH)2D3 in binding to the chick intestinal receptor for 1,25(OH)2D3. Thus receptor discrimination may account for the twofold difference in intestinal calcium transport activity. 24-Epi-1,25(OH)2D2 appeared inactive in in vivo mobilization of bone calcium or bone phosphorus. On the other hand, in fetal rat bone in culture, the epi compound was only five times less active than 1,25(OH)2D2 in inducing resorption. Short-term experiments on bone mineral mobilization in vivo show that the 24-epi-1,25(OH)2D2 does induce bone calcium mobilization but that its activity in this respect is short lived. It is suggested that 24-epi-1,25(OH)2D2 and, as a result, it shows preferential activity on intestine whose response to a single dose of 1,25(OH)2D2 remains for several days, whereas the short-lived bone system does not remain stimulated during the 24-h period between doses.

Animals↗
PubMed1988

Analogs of the hormonal form of vitamin D and their possible use in leukemia.

We have concluded a large analog study that suggests that specific analogs of 1,25-(OH)2D3 can be prepared that have markedly enhanced activity in promoting differentiation of HL-60 promyelocytes to benign monocytes. We have observed that lengthening the side chain of 1,25-(OH)2D3 increases activity in HL-60 by 1 order of magnitude when the side chain is increased in length by 1 carbon. At the same time, the biological activity of these compounds in serum calcium elevation is either unchanged or diminished. Thus, lengthening the side chain may well provide a preferentially active form of vitamin D on the promyelocytes. Shortening the side chain has resulted a 10-fold loss of activity in HL-60 for each carbon removed. Furthermore, elimination of the 26- and 27-carbons decreases biological activity by 100-fold. If, however, the hydroxyl is left off the side chain and small hydrocarbon side chains of ethyl or isopropyl are substituted, very high activity in HL-60 is achieved without activity in mobilizing calcium in vivo. We, therefore, have compounds in hand which illustrate at least in vitro specific activity in HL-60.

Animals↗
PubMed1988

Vitamin D metabolites and bioactive parathyroid hormone levels during Spacelab 2.

The purpose of this study was to determine whether plasma levels of the vitamin D hormone and parathyroid hormone (PTH), two potent activators of bone remodeling sites, were altered in four astronauts during the 8-day (d) Spacelab 2 mission (SL2). Increased circulating levels of either hormone could change calcium homeostasis and bone cell activity and, thus, contribute to bone loss in crewmembers in space. The vitamin D hormone was elevated in all astronauts at the end of the first inflight day but returned to normal by the seventh day. Biologically active PTH tended to be normal throughout the mission. Both hormones were within the normal range by the end of the 8-d flight of this SL2 crew. Plasma levels of 25OHD, 24,25(OH)2D, calcium, phosphorus, and albumin were essentially normal during the mission.

24,25-Dihydroxyvitamin D 3↗