The calcimimetic R-568 increases vitamin D receptor expression in rat parathyroid glands

2007 ◽  
Vol 292 (5) ◽  
pp. F1390-F1395 ◽  
Author(s):  
M. E. Rodriguez ◽  
Y. Almaden ◽  
S. Cañadillas ◽  
A. Canalejo ◽  
E. Siendones ◽  
...  
Keyword(s):  
Vitamin D ◽  
Vitamin D Receptor ◽  
Parathyroid Tissue ◽  
Receptor Expression ◽  
Parathyroid Glands ◽  
In Vivo Studies ◽  
Control Treatment ◽  
Maximum Increase

We previously demonstrated that extracellular calcium regulates vitamin D receptor (VDR) expression by parathyroid cells. Since the calcimimetic R-568 potentiates the effects of calcium on the calcium-sensing receptor, it was hypothesized that administration of R-568 may result in increased VDR expression in parathyroid tissue. In vitro studies of the effect of R-568 on VDR mRNA and protein were conducted in cultures of whole rat parathyroid glands and human hyperplastic parathyroid glands. In vivo studies in Wistar rats examined the effect of R-568 and calcitriol alone and in combination. Incubation of rat parathyroid glands in vitro with R-568 (0.001–1 μM) resulted in a dose-dependent decrease in parathyroid hormone (PTH) secretion and an increase in VDR expression (mean ± SE). Incubation in 1 mM calcium + 0.001 μM R-568 elicited an increase in VDR mRNA (306 ± 46%) similar to the maximum increase detected with 1.5 mM calcium (330 ± 42%). In vivo, VDR mRNA was increased after administration of R-568 (168 ± 9%, P < 0.001 vs. control) or calcitriol (198 ± 16%, P < 0.001 vs. control). Treatment with R-568 also increased VDR protein in normal rat parathyroid glands and in human parathyroid glands with diffuse, but not nodular, hyperplasia. In conclusion, the present study shows that the calcimimetic R-568 exerts a stimulatory effect on VDR expression in the parathyroid glands of study models and provides additional evidence for the use of calcimimetics in the treatment of secondary hyperparathyroidism.

scholarly journals The Efficacy of Nanoemulsion-Based Delivery to Improve Vitamin D Absorption: Comparison of In Vitro and In Vivo Studies

2018 ◽  
Vol 62 (4) ◽  
pp. 1700836 ◽  
Author(s):  
Alagu Selvi Kadappan ◽  
Chi Guo ◽  
Cansu E. Gumus ◽  
Amy Bessey ◽  
Richard J. Wood ◽  
...  
Keyword(s):  
Vitamin D ◽  
In Vivo Studies

scholarly journals 1,25-Dihydroxy-19-nor-vitamin D2, a Vitamin D Analog with Reduced Bone Resorbing Activity In Vitro

2000 ◽  
Vol 11 (10) ◽  
pp. 1857-1864
Author(s):  
L. SHANNON HOLLIDAY ◽  
STEPHEN L. GLUCK ◽  
EDUARDO SLATOPOLSKY ◽  
ALEX J. BROWN
Keyword(s):  
Vitamin D ◽  
Acid Phosphatase ◽  
Bone Resorption ◽  
Vitamin D Receptor ◽  
Intrinsic Activity ◽  
Tartrate Resistant Acid Phosphatase ◽  
Mouse Bone Marrow ◽  
Bone Resorbing Activity

Abstract. 1,25-Dihydroxy-19-nor-vitamin D2 (19-norD2), a new analog of 1,25(OH)2D3, suppresses parathyroid hormone in renal failure patients and in uremic rats but has less calcemic activity than 1,25(OH)2D3. Although 19-norD2 has high affinity for the vitamin D receptor and similar pharmacokinetics to those of 1,25(OH)2D3, it has much less bone resorbing activity in vivo. The intrinsic activity of 19-norD2 on osteoclastogenesis and activation of bone resorption in mouse bone marrow cultures was examined to determine the mechanism involved. 19-norD2 and 1,25(OH)2D3 (10 nM) were equivalent in stimulating the formation and maintenance of large multinucleated, tartrate-resistant acid phosphatase-positive cells. However, the amount of bone resorbed by osteoclasts stimulated by 10 nM 19-norD2, as measured by pit-forming assays, was reduced 62% compared with 10 nM 1,25(OH)2D3-stimulated osteoclasts (P < 0.05). This difference could not be attributed to enhanced catabolism or to downregulated vitamin D receptor. The rate of degradation of 19-norD2 in cultures was approximately 20% greater than 1,25(OH)2D3, not enough to account for the different effects on bone resorption. The VDR levels were identical in cultures that were treated with 19-norD2 and 1,25(OH)2D3. In summary, 19-norD2 is less effective than 1,25(OH)2D3 in stimulating mouse marrow osteoclasts to resorb bone. The reason for this difference is not clear but seems to involve the late maturation and/or activation of osteoclasts as the number of pits produced by each tartrate-resistant acid phosphatase-positive cell is reduced under stimulation by 19-norD2 compared with 1,25(OH)2D3.

scholarly journals Vitamin D and prostate cancer

2013 ◽  
Vol 66 (5-6) ◽  
pp. 259-262
Author(s):  
Goran Marusic ◽  
Dimitrije Jeremic ◽  
Sasa Vojinov ◽  
Natasa Filipovic ◽  
Milan Popov
Keyword(s):  
Prostate Cancer ◽  
Vitamin D ◽  
Physiological Role ◽  
In Vivo Studies ◽  
Vitamin D Metabolism ◽  
Genetic Changes ◽  
Metabolic Role

In addition to the metabolic role of vitamin D, which is well known and clearly defined, there have been many hypotheses regarding its anti-proliferative and pro-apoptotic role. Epidemiology and Significance of Prostate Cancer. Prostate cancer is the second most common malignancy in men. Long period of cancerogenesis, available tumor markers and high incidence make this cancer ideal for preventive measures. Physiological Role of Vitamin D and its Effect on Prostate Cancer Cells. In vitro and in vivo studies have shown the anti-proliferative and pro-apoptopic role of vitamin D. Disorders of vitamin D metabolism are noted in vitamin D gene level, vitamin D receptor, vitamin D responsive elements and androgen receptors. We present the most important effect of those changes on vitamin D metabolism. Conclusion. Available studies on vitamin D level in serum, prostate tissue, observed activity of vitamin D enzymes and genetic changes give us only a slight insight into the basic mechanisms of vitamin D action in the development of prostate cancer; therefore, further investigations are needed.

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.

scholarly journals The Vitamin D Receptor Is Present in Caveolae-Enriched Plasma Membranes and Binds 1α,25(OH)2-Vitamin D3in Vivo and in Vitro

2004 ◽  
Vol 18 (11) ◽  
pp. 2660-2671 ◽  
Author(s):  
Johanna A. Huhtakangas ◽  
Christopher J. Olivera ◽  
June E. Bishop ◽  
Laura P. Zanello ◽  
Anthony W. Norman
Keyword(s):  
Vitamin D ◽  
Plasma Membrane ◽  
Vitamin D Receptor ◽  
Plasma Membranes ◽  
Binding Protein ◽  
Kidney Tissue ◽  
Mouse Lung ◽  
Nuclear Fraction

Abstract The steroid hormone 1α,25(OH)2-vitamin D3 (1,25D) regulates gene transcription through a nuclear receptor [vitamin D receptor (VDR)] and initiation of rapid cellular responses through a putative plasma membrane-associated receptor (VDRmem). This study characterized the VDRmem present in a caveolae-enriched membrane fraction (CMF), a site of accumulation of signal transduction agents. Saturable and specific [3H]-1,25D binding in vitro was found in CMF of chick, rat, and mouse intestine; mouse lung and kidney; and human NB4 leukemia and rat ROS 17/2.8 osteoblast-like cells; in all cases the 1,25D KD binding dissociation constant = 1–3 nm. Our data collectively support the classical VDR being the VDRmem in caveolae: 1) VDR antibody immunoreactivity was detected in CMF of all tissues tested; 2) competitive binding of [3H]-1,25D by eight analogs of 1,25D was significantly correlated between nuclei and CMF (r2 = 0.95) but not between vitamin D binding protein (has a different ligand binding specificity) and CMF; 3) confocal immunofluorescence microscopy of ROS 17/2.8 cells showed VDR in close association with the caveolae marker protein, caveolin-1, in the plasma membrane region; 4) in vivo 1,25D pretreatment reduced in vitro [3H]-1,25D binding by 30% in chick and rat intestinal CMF demonstrating in vivo occupancy of the CMF receptor by 1,25D; and 5) comparison of [3H]-1,25D binding in VDR KO and WT mouse kidney tissue showed 85% reduction in VDR KO CMF and 95% reduction in VDR KO nuclear fraction. This study supports the presence of VDR as the 1,25D-binding protein associated with plasma membrane caveolae.

scholarly journals Intraoperative Autofluorescence and Indocyanine Green Angiography for the Detection and Preservation of Parathyroid Glands

2020 ◽  
Vol 9 (3) ◽  
pp. 830 ◽  
Author(s):  
Marco Stefano Demarchi ◽  
Wolfram Karenovics ◽  
Benoît Bédat ◽  
Frédéric Triponez
Keyword(s):  
Thyroid Surgery ◽  
Near Infrared ◽  
Infrared Imaging ◽  
Parathyroid Tissue ◽  
Parathyroid Glands ◽  
Endocrine Surgery ◽  
Near Infrared Imaging ◽  
Postoperative Hypoparathyroidism

Fluorescence imaging is a well-known method for both the in vivo and in vitro identification of specific cells or tissues. This imaging tool is gaining importance in the intraoperative detection and preservation of parathyroid glands during endocrine surgery owing to the intrinsic properties of parathyroid tissue. The aim of this paper is to provide an overview of the basics of the technology, its history, and the recent surgical intraoperative applications of near-infrared imaging methods. Moreover, a literature review of the utilization of fluorescence devices in thyroid surgery suggests that the use of near-infrared imaging seems to be beneficial in reducing postoperative hypoparathyroidism, which is one of the most frequent complications of thyroid surgery.

scholarly journals In Vitro and In Vivo Analysis of the Immune System of Vitamin D Receptor Knockout Mice

2001 ◽  
Vol 16 (11) ◽  
pp. 2057-2065 ◽  
Author(s):  
Chantal Mathieu ◽  
Evelyne Van Etten ◽  
Conny Gysemans ◽  
Brigitte Decallonne ◽  
Shigeaki Kato ◽  
...  
Keyword(s):  
Vitamin D ◽  
Immune System ◽  
Vitamin D Receptor ◽  
Knockout Mice ◽  
In Vivo Analysis

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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