A monolog on analogs: In vitro effects of vitamin D metabolites and consideration of the mineralization question

1981 ◽  
Vol 33 (1) ◽  
pp. 1-4 ◽  
Author(s):  
Paula H. Stern
Keyword(s):  
Vitamin D ◽  
Vitamin D Metabolites ◽  
In Vitro Effects

scholarly journals Epimers of Vitamin D: A Review

2020 ◽  
Vol 21 (2) ◽  
pp. 470 ◽  
Author(s):  
Bashar Al-Zohily ◽  
Asma Al-Menhali ◽  
Salah Gariballa ◽  
Afrozul Haq ◽  
Iltaf Shah
Keyword(s):  
Vitamin D ◽  
Biological Activity ◽  
Hydroxyl Group ◽  
Vitamin D Metabolites ◽  
Dihydroxyvitamin D3 ◽  
In Vivo Models ◽  
Vitamin D Receptors ◽  
Potential Factors

In this review, we discuss the sources, formation, metabolism, function, biological activity, and potency of C3-epimers (epimers of vitamin D). We also determine the role of epimerase in vitamin D-binding protein (DBP) and vitamin D receptors (VDR) according to different subcellular localizations. The importance of C3 epimerization and the metabolic pathway of vitamin D at the hydroxyl group have recently been recognized. Here, the hydroxyl group at the C3 position is orientated differently from the alpha to beta orientation in space. However, the details of this epimerization pathway are not yet clearly understood. Even the gene encoding for the enzyme involved in epimerization has not yet been identified. Many published research articles have illustrated the biological activity of C3 epimeric metabolites using an in vitro model, but the studies on in vivo models are substantially inadequate. The metabolic stability of 3-epi-1α,25(OH)2D3 has been demonstrated to be higher than its primary metabolites. 3-epi-1 alpha, 25 dihydroxyvitamin D3 (3-epi-1α,25(OH)2D3) is thought to have fewer calcemic effects than non-epimeric forms of vitamin D. Some researchers have observed a larger proportion of total vitamin D as C3-epimers in infants than in adults. Insufficient levels of vitamin D were found in mothers and their newborns when the epimers were not included in the measurement of vitamin D. Oral supplementation of vitamin D has also been found to potentially cause increased production of epimers in mice but not humans. Moreover, routine vitamin D blood tests for healthy adults will not be significantly affected by epimeric interference using LC–MS/MS assays. Recent genetic models also show that the genetic determinants and the potential factors of C3-epimers differ from those of non-C3-epimers.Most commercial immunoassays techniques can lead to inaccurate vitamin D results due to epimeric interference, especially in infants and pregnant women. It is also known that the LC–MS/MS technique can chromatographically separate epimeric and isobaric interference and detect vitamin D metabolites sensitively and accurately. Unfortunately, many labs around the world do not take into account the interference caused by epimers. In this review, various methods and techniques for the analysis of C3-epimers are also discussed. The authors believe that C3-epimers may have an important role to play in clinical research, and further research is warranted.

Renal effect of vitamin D metabolites: evidence for the essential role of the 25(OH) group

1983 ◽  
Vol 244 (6) ◽  
pp. F674-F678 ◽  
Author(s):  
M. M. Friedlaender ◽  
Z. Kornberg ◽  
H. Wald ◽  
M. M. Popovtzer
Keyword(s):  
Vitamin D ◽  
Vitamin D3 ◽  
Essential Role ◽  
Fractional Excretion ◽  
Vitamin D Metabolites ◽  
Group 2 ◽  
Fractional Excretion Of Phosphate ◽  
Group 1

The effects of 1 alpha (OH)vitamin D3 [1 alpha (OH)D3] and 24,25(OH)2vitamin D3 [24,25(OH)2D3] on the phosphaturic action of parathyroid hormone (PTH) were studied in two groups of parathyroidectomized (PTX) rats. In group 1, PTX PTH-infused rats received intravenous 1 alpha (OH)D3, and in group 2, PTX PTH-infused rats received intravenous 24,25(OH)2D3. PTX PTH-infused rats served as controls. The effects of both vitamin D metabolites on renal PTH-activated adenylate cyclase (AC) were studied in vitro. In group 1, PTH increased fractional excretion of phosphate (CP/CIn) from 0.045 +/- 0.012 (+/- SE) to 0.263 +/- 0.011 (P less than 0.005). 1 alpha (OH)D3 failed to influence this response. In group 2, PTH increased CP/CIn from 0.055 +/- 0.008 to 0.289 +/- 0.027 (P less than 0.005). 24,25(OH)2D3 reduced the PTH-induced rise in CP/CIn from 0.289 +/- 0.027 to 0.192 +/- 0.021 (P less than 0.01) and decreased the urinary excretion of adenosine 3',5'-cyclic monophosphate. In vitro, 24,25(OH)2D3 blunted the PTH-activated AC, whereas 1 alpha (OH)D3 had no effect. These results show that 24,25(OH)D3, similar to two other 25(OH) metabolites of vitamin D-25(OH)vitamin D3 and 1,25(OH)2vitamin D3-suppresses the phosphaturic action of PTH, whereas 1 alpha(OH)D3, which is devoid of a 25(OH) group, lacks this effect. This suggests that a 25(OH) group is a prerequisite for the antiphosphaturic effect of vitamin D, whereas the 1 alpha (OH) group is not essential for this action.

Effects of 1,25- and 24,25-dihydroxycholecalciferol on parathyroid hormone release from human parathyroid cells in vitro

1984 ◽  
Vol 105 (3) ◽  
pp. 354-359 ◽  
Author(s):  
Claes Rudberg ◽  
Göran Åkerström ◽  
Henry Johansson ◽  
Sverker Ljunghall ◽  
Jan Malmaeus ◽  
...  
Keyword(s):  
Vitamin D ◽  
Parathyroid Hormone ◽  
Parathyroid Tissue ◽  
Vitamin D Metabolites ◽  
Hormone Release ◽  
High Doses ◽  
Parathyroid Hormone Release ◽  
Dispersed Cells

Abstract. The effects of 125-dihydroxycholecalciferol (1,25-(OH)2D3) and 24,25-dihydroxycholecalciferol (24,25-(OH)2D3) on parathyroid hormone (PTH) release from human parathyroid cells were investigated using an in vitro system of dispersed cells. The cells were obtained from 7 patients with primary hyperparathyroidism (HPT) and adenoma, 4 patients with primary HPT due to hyperplasia and 2 patients with parathyroid hyperplasia secondary to chronic renal failure. The dispersed cells were incubated in tissue culture medium at low, normal and high external calcium concentrations for 2–16 h. There was a gradual suppression of PTH release (5–55%) when the calcium concentration in the medium was increased from 0.5 to 3.0 mM, thus indicating retained regulation of hormone release. The addition of 1,25-(OH)2D3 in concentrations of 0.1 and 1 ng/ml and of 24,25-(OH)2D3 in concentrations of 1.0 and 10 ng/ml during the incubations did not further affect the amount of PTH released by the cells. The concentrations of the different vitamin D metabolites tested closely correspond to levels observed under normal physiological conditions and during treatment with high doses of vitamin D in vivo. Thus, the findings contradict the idea of any direct short-term regulatory effect of either 1,25-(OH)2D3 or 24,25-(OH)2D3 on the secretion of PTH from hyperfunctioning human parathyroid tissue.

Vitamin D metabolites regulate osteocalcin synthesis and proliferation of human bone cells in vitro

1985 ◽  
Vol 105 (3) ◽  
pp. 391-396 ◽  
Author(s):  
H. Skjødt ◽  
J. A. Gallagher ◽  
J. N. Beresford ◽  
M. Couch ◽  
J. W. Poser ◽  
...  
Keyword(s):  
Vitamin D ◽  
Cell Proliferation ◽  
Bone Cells ◽  
Rank Order ◽  
Human Bone ◽  
Dependent Manner ◽  
Vitamin D Metabolites ◽  
Hydroxyvitamin D ◽  
Dihydroxyvitamin D

ABSTRACT The effects of six natural vitamin D metabolites of potential biological and therapeutic interest, 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3), 25-hydroxyvitamin D3 (25-OH-D3), 24R,25-dihydroxyvitamin D3 (24R,25-(OH)2D3), 1,24R,25-trihydroxyvitamin D3 (1,24R,25-(OH)3D3), 25S,26-dihydroxyvitamin D3 (25S,26-(OH)2D3) and 1,25S,26-trihydroxyvitamin D3 (1,25S,26-(OH)3D3) on cell replication and expression of the osteoblastic phenotype in terms of osteocalcin production were examined in cultured human bone cells. At a dose of 5 × 10−12 mol/l, 1,25-(OH)2D3 stimulated cell proliferation, whereas at higher doses (5 × 10−9−5 × 10 −6 mol/l) cell growth was inhibited in a dose-dependent manner. The same pattern of effects was seen for the other metabolites in a rank order of potency: 1,25-(OH)2D3> 1,25S,26-(OH)3D3 = 1,24R,25-(OH)3D3>25S,26-(OH)2D3 = 24R,25-(OH)2D3 = 25-OH-D3. Synthesis of osteocalcin was induced by 1,25-(OH)2D3 in doses similar to those required to inhibit cell proliferation. Biphasic responses were observed for some of the metabolites in terms of osteocalcin synthesis, inhibitory effects becoming apparent at 5 × 10−6 mol/l. The cells did not secrete osteocalcin spontaneously. These results indicate that vitamin D metabolites may regulate growth and expression of differentiated functions of normal human osteoblasts. J. Endocr. (1985) 105, 391–396

Early effects of vitamin D metabolites on phosphate fluxes in isolated rat enterocytes

1985 ◽  
Vol 248 (1) ◽  
pp. G40-G45 ◽  
Author(s):  
G. Karsenty ◽  
B. Lacour ◽  
A. Ulmann ◽  
E. Pierandrei ◽  
T. Drueke
Keyword(s):  
Vitamin D ◽  
Vitamin D3 ◽  
Vitamin D Metabolites ◽  
Dihydroxyvitamin D3 ◽  
Nongenomic Action ◽  
Efflux Rate Constant ◽  
Membrane Effects ◽  
Uptake Velocity ◽  
Vitro Effect

The present studies were designed to explore the possibility that, in addition to its well-known steroidlike action, 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], the active vitamin D3 metabolite, modulates inorganic phosphate (Pi) transport across the intestinal mucosa through more rapid membrane effects. Enterocytes were mechanically isolated from the duodenojejunum of vitamin D-replete rats. In this model enterocyte Pi uptake was a temperature-dependent as well as a Na+-dependent process. In vitro addition of 1,25(OH)2D3 (1 pM) led to a significant increase in Na+-dependent initial Pi uptake velocity (iVpi) within 20 min (P less than 0.001). No effect was seen for shorter incubation times (5 and 15 min). Incubation of the cells with cycloheximide did not inhibit the hormone-mediated increase of iVpi. 25-Hydroxyvitamin D3 significantly increased iVPi (P less than 0.05) at a concentration of 1 nM but not 1 pM. Vitamin D3 at a concentration of 1 microM had no effect on iVPi. Enterocyte Pi efflux rate constant was not modified by the presence of 1,25(OH)2D3(1pM). Thus, the early in vitro effect of 1,25(OH)2D3 on Pi uptake by isolated enterocytes suggests a nongenomic action of the hormone, possibly by modifying the lipid structure of the plasma membrane.

scholarly journals Electrochemical Oxidation as a Tool for Generating Vitamin D Metabolites

Molecules ◽  
2019 ◽  
Vol 24 (13) ◽  
pp. 2369 ◽  
Author(s):  
Navarro Suarez ◽  
Thein ◽  
Kallinich ◽  
Rohn
Keyword(s):  
Vitamin D ◽  
Phase Ii ◽  
Animal Studies ◽  
Ph Value ◽  
Oxidation Products ◽  
In Vitro Test ◽  
Vitamin D Metabolites ◽  
Constant Potential

The electrochemical behavior of the vitamers cholecalciferol and ergocalciferol was investigated in order to determine whether it is possible to evaluate phase-I and phase-II metabolism of these steroids and yield metabolites that can serve as reference material. The vitamers were electrochemically-oxidized using an electrochemical system (ROXY™ EC system). The influence of pH value, solvent, and potential was evaluated. When using methanol or ethanol, the formation of artificial methoxy or ethoxy groups, respectively, was observed, while the use of acetonitrile did not show any formation of further functional groups. A neutral pH value and use of a constant potential led to the highest number of oxidation products with intensive signals. Additionally, a binding study between vitamin D and glucuronic acid as an example for phase-II conjugation was carried out. It was possible to detect adduct formation. Coupling mass spectrometry directly to electrochemistry (EC-MS) is a promising approach for generating vitamin D metabolites and/or yielding a number of metabolites without in vivo or in vitro test systems. It can support or even replace animal studies in the long-term and might be promising for yielding reference compounds.

scholarly journals The Pleiotropic Effects of Vitamin D in Gynaecological and Obstetric Diseases: An Overview on a Hot Topic

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Francesca Colonese ◽  
Antonio Simone Laganà ◽  
Elisabetta Colonese ◽  
Vincenza Sofo ◽  
Francesca Maria Salmeri ◽  
...  
Keyword(s):  
Vitamin D ◽  
Metabolic Pathways ◽  
Polycystic Ovary ◽  
Serum Levels ◽  
In Vivo Studies ◽  
Vitamin D Metabolites ◽  
Vitamin D Metabolism ◽  
Vitamin D Levels

The traditionally recognized role of vitamin D consists in the regulation of bone metabolism and calcium-phosphorus homeostasis but recently a lot of in vitro and in vivo studies recognized several “noncalcemic” effects of vitamin D metabolites. Accumulating evidence suggests that the metabolic pathways of this vitamin may play a key role in the developing of gynaecological/obstetric diseases. VDR-mediated signalling pathways and vitamin D levels seem to (deeply) affect the risk of several gynaecological diseases, such as polycystic ovary syndrome (PCOS), endometriosis, and ovarian and even breast cancer. On the other hand, since also the maternal-fetal unit is under the influence of vitamin D, a breakdown in its homeostasis may underlie infertility, preeclampsia, and gestational diabetes mellitus (GDM). According to our literature review, the relationship between vitamin D and gynaecological/obstetric diseases must be replicated in future studies which could clarify the molecular machineries behind their development. We suggest that further investigation should take into account the different serum levels of this vitamin, the several actions which arise from the binding between it and its receptor (taking into account its possible polymorphism), and finally the interplay between vitamin D metabolism and other hormonal and metabolic pathways.

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