Vitamin D metabolism in aged Japanese quail: dietary calcium and estrogen effects

1981 ◽  
Vol 241 (4) ◽  
pp. E275-E280
Author(s):  
S. N. Baksi ◽  
A. D. Kenny

The influence of estrogen treatment (estradiol benzoate, 1 mg/kg daily for 5 days) on the in vitro renal metabolism of 25-[3H]hydroxyvitamin D3 has been studied in young adult (8-wk-old) and aged (108-wk-old) female and male Japanese quail maintained either on a normal calcium diet or on a low-calcium diet for 4 wk. It is concluded that senescence leads to reduced production of 1,25-dihydroxyvitamin D2 [1,25(OH)2D3] in untreated birds of both sexes and under both dietary conditions. Nevertheless, the renal vitamin D-endocrine system in aged birds has the capacity, when stimulated under appropriate conditions (estradiol-treated, calcium-deprived aged males), for operating at a very high production rate (315 +/- 21 pmol . min-1 . g kidney-1). The latter rate is not far below the maximal rate (393 +/- 25 pmol . min-1 . g kidney-1) observed in young adult birds that had been stimulated by calcium deprivation.

1984 ◽  
Vol 101 (3) ◽  
pp. 333-338 ◽  
Author(s):  
N. Wongsurawat ◽  
H. J. Armbrecht ◽  
T. V. Zenser ◽  
L. R. Forte ◽  
B. B. Davis

ABSTRACT Growth hormone stimulates intestinal calcium absorption. This action has been linked to vitamin D metabolism. We have investigated the effects of hypophysectomy and GH treatment on renal metabolism of 25-hydroxycholecalciferol (25-OH-D3). Renal hydroxylation of 25-OH-D3 was measured in vitro using the renal slice technique. Experiments were performed in young F344 rats fed a vitamin D-replete, low calcium diet for 4 weeks. In hypophysectomized rats, renal conversion of 25-OH-D3 to 1,25-dihydroxycholecalciferol (1,25-(OH)2D3) was markedly reduced compared with sham-operated rats. Renal conversion of 25-OH-D3 to 24,25-(OH)2D3 was markedly increased in hypophysectomized rats compared with sham-operated rats. Treatment of hypophysectomized rats with rat GH (rGH) for 10 days resulted in a significant increase in renal conversion of 25-OH-D3 to 1,25-(OH)2D3 and a significant decrease in conversion to 24,25-(OH)2D3. Rat GH treatment caused no significant changes in serum levels of immunoreactive parathyroid hormone. Serum calcium concentrations were similar in all groups, and serum phosphorus was low in hypophysectomized rats. Treatment of hypophysectomized rats with ovine GH for 6 days caused changes which were much less pronounced than those induced by rGH. Renal conversion of 25-OH-D3 to 1,25-(OH)2D3 and 24,25-(OH)2D3 correlated well with growth rate (weight gain). These results suggest that GH, either directly or indirectly, modulates renal metabolism of 25-OH-D3. J. Endocr. (1984) 101, 333–338


2005 ◽  
Vol 289 (1) ◽  
pp. F8-F28 ◽  
Author(s):  
Adriana S. Dusso ◽  
Alex J. Brown ◽  
Eduardo Slatopolsky

The vitamin D endocrine system plays an essential role in calcium homeostasis and bone metabolism, but research during the past two decades has revealed a diverse range of biological actions that include induction of cell differentiation, inhibition of cell growth, immunomodulation, and control of other hormonal systems. Vitamin D itself is a prohormone that is metabolically converted to the active metabolite, 1,25-dihydroxyvitamin D [1,25(OH)2D]. This vitamin D hormone activates its cellular receptor (vitamin D receptor or VDR), which alters the transcription rates of target genes responsible for the biological responses. This review focuses on several recent developments that extend our understanding of the complexities of vitamin D metabolism and actions: the final step in the activation of vitamin D, conversion of 25-hydroxyvitamin D to 1,25(OH)2D in renal proximal tubules, is now known to involve facilitated uptake and intracellular delivery of the precursor to 1α-hydroxylase. Emerging evidence using mice lacking the VDR and/or 1α-hydroxylase indicates both 1,25(OH)2D3-dependent and -independent actions of the VDR as well as VDR-dependent and -independent actions of 1,25(OH)2D3. Thus the vitamin D system may involve more than a single receptor and ligand. The presence of 1α-hydroxylase in many target cells indicates autocrine/paracrine functions for 1,25(OH)2D3in the control of cell proliferation and differentiation. This local production of 1,25(OH)2D3is dependent on circulating precursor levels, providing a potential explanation for the association of vitamin D deficiency with various cancers and autoimmune diseases.


1960 ◽  
Vol 198 (2) ◽  
pp. 269-274 ◽  
Author(s):  
Eugene B. Dowdle ◽  
David Schachter ◽  
Harris Schenker

The active transport of calcium from the mucosal to the serosal surfaces of everted gut-sacs of the rat is dependent on the dietary vitamin D. The active transfer in vitro is significantly increased one hour following the administration of calciferol by gastric tube to rats depleted of the vitamin. Vitamins D2 and D3 are approximately equally effective, whereas dihydrotachysterol (A.T. 10) is somewhat more effective than either of the vitamins D. Ultraviolet irradiation of intact rats also increases the active transport of calcium in vitro. Maintenance on a low calcium diet increases the active transfer, whereas thyroparathyroidectomy decreases it. Vitamin D is required to demonstrate both of these effects clearly. The results support the hypothesis that the active transfer is an adaptive mechanism which ensures adequate absorption when the requirement for calcium is increased, or when the diet is low in calcium.


Endocrinology ◽  
2007 ◽  
Vol 148 (3) ◽  
pp. 1396-1402 ◽  
Author(s):  
Yurong Song ◽  
James C. Fleet

We tested the hypothesis that low vitamin D receptor (VDR) level causes intestinal vitamin D resistance and intestinal calcium (Ca) malabsorption. To do so, we examined vitamin D regulated duodenal Ca absorption and gene expression [transient receptor potential channel, vallinoid subfamily member 6 (TRPV6), 24-hydroxylase, calbindin D9k (CaBP) mRNA, and CaBP protein] in wild-type mice and mice with reduced tissue VDR levels [i.e. heterozygotes for the VDR gene knockout (HT)]. Induction of 24-hydroxylase mRNA levels by 1,25 dihydroxyvitamin D3 [1,25(OH)2 D3] injection was significantly reduced in the duodenum and kidney of HT mice in both time-course and dose-response experiments. TRPV6 and CaBP mRNA levels in duodenum were significantly induced after 1,25(OH)2 D3 injection, but there was no difference in response between wild-type and HT mice. Feeding a low-calcium diet for 1 wk increased plasma PTH, renal 1α-hydroxylase (CYP27B1) mRNA level, and plasma 1,25(OH)2 D3, and this response was greater in HT mice (by 88, 55, and 37% higher, respectively). In contrast, duodenal TRPV6 and CaBP mRNA were not higher in HT mice fed the low-calcium diet. However, the response of duodenal Ca absorption and CaBP protein to increasing 1,25(OH)2 D3 levels was blunted by 40% in HT mice. Our data show that low VDR levels lead to resistance of intestinal Ca absorption to 1,25(OH)2 D3, and this resistance may be due to a role for the VDR (and VDR level) in the translation of CaBP.


Endocrinology ◽  
2011 ◽  
Vol 152 (3) ◽  
pp. 1195-1195
Author(s):  
Carlo Foresta ◽  
Giacomo Strapazzon ◽  
Luca De Toni ◽  
Lisa Perilli ◽  
Antonella Di Mambro ◽  
...  

Abstract Working Hypothesis: Mutations in the CYP2R1 gene, highly expressed in the testis and encoding vitamin D 25-hydroxylase, result in a vitamin D deficiency and a defective calcium homeostasis leading to rickets. Objective: Our aim was to investigate CYP2R1 expression in pathological testis samples and relate this to vitamin D metabolism in testiculopathic patients. Design, Patients, Setting: Testis samples for in vitro study and 98 young men were transversally evaluated at Padova's Center for Male Gamete Cryopreservation. Methods: CYP2R1 mRNA expression and protein production were evaluated by quantitative RT-PCR, Western blot analysis, and immunofluorescence. Hormonal and bone-marker levels, and bone densitometry by dual-energy x-ray absorptiometry, were determined in patients with Sertoli-cell-only syndrome and severe hypospermatogenesis. Results: We found a lower gene and protein expression of CYP2R1 in samples with hypospermatogenesis and Sertoli-cell-only syndrome (P < 0.05) and a colocalization with INSL-3, a Leydig cell marker, at immunofluorescence. In all testiculopathic patients 25-hydroxyvitamin D levels were significantly lower and PTH levels higher compared to controls (P < 0.05). Furthermore, testiculopathic patients showed osteopenia and osteoporosis despite normal testosterone levels compared with controls both with increased bone-marker levels and altered dual-energy x-ray absorptiometry in the femoral neck and lumbar spine (for all parameters, P < 0.05). Conclusions: Our data show an association between testiculopathy and alteration of the bone status, despite unvaried androgen and estrogen levels and no other evident cause of vitamin D reduction. Further studies in larger cohorts are needed to confirm our results.


2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Sarah A. Howles ◽  
Akira Wiberg ◽  
Michelle Goldsworthy ◽  
Asha L. Bayliss ◽  
Anna K. Gluck ◽  
...  

AbstractKidney stone disease (nephrolithiasis) is a major clinical and economic health burden with a heritability of ~45–60%. We present genome-wide association studies in British and Japanese populations and a trans-ethnic meta-analysis that include 12,123 cases and 417,378 controls, and identify 20 nephrolithiasis-associated loci, seven of which are previously unreported. A CYP24A1 locus is predicted to affect vitamin D metabolism and five loci, DGKD, DGKH, WDR72, GPIC1, and BCR, are predicted to influence calcium-sensing receptor (CaSR) signaling. In a validation cohort of only nephrolithiasis patients, the CYP24A1-associated locus correlates with serum calcium concentration and a number of nephrolithiasis episodes while the DGKD-associated locus correlates with urinary calcium excretion. In vitro, DGKD knockdown impairs CaSR-signal transduction, an effect rectified with the calcimimetic cinacalcet. Our findings indicate that studies of genotype-guided precision-medicine approaches, including withholding vitamin D supplementation and targeting vitamin D activation or CaSR-signaling pathways in patients with recurrent kidney stones, are warranted.


2013 ◽  
Vol 66 (5-6) ◽  
pp. 259-262
Author(s):  
Goran Marusic ◽  
Dimitrije Jeremic ◽  
Sasa Vojinov ◽  
Natasa Filipovic ◽  
Milan Popov

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.


2007 ◽  
Vol 6 (1) ◽  
pp. 48-55 ◽  
Author(s):  
Jörg Reichrath ◽  
Martin Rech ◽  
Maryam Moeini ◽  
Eckart Meese ◽  
Wolfgang Tilgen ◽  
...  

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