25-Hydroxyvitamin D3-1 alpha-hydroxylase in porcine hepatic tissue: subcellular localization to both mitochondria and microsomes.

Hollis, Bruce W.

doi:10.1073/pnas.87.16.6009

Cited by 34 publications

(18 citation statements)

References 46 publications

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“…In our present study, we not only searched for evidence of local production of l,25(OH)2D3 by the fetal hepatocytes but also investigated the effect of l,25(OH)2D3 on the growth of these actively proliferating cells. Our studies using 19-day gestation fetal rat hepatocytes did not demonstrate any l,25(OH)2D3 production in contrast to data reported by Hollis [12] using porcine liver. The difference in the development state of the cells (fetal cells in our experiments vs. those from 3-month-old piglets) may explain these contrasting findings.…”

Section: Resultscontrasting

confidence: 56%

“…in the liver are probably me diated through its interaction with its specific intracellular receptor, the presence of which has been demonstrated in both the mammali an and avian adult liver [11], Fetal hepatocytes, like regenerating hepatocytes, are ac tively proliferating cells. It has recently been demonstrated that the neonatal porcine liver [ 12] and the adult rat liver [ 13] have the enzy matic ability to convert 25-hydroxyvitamin D3 (25-OH D 3) to 1,25(OH)2D3. We used fetal hepatocytes as a model cell line to test the hypothesis that the fetal liver locally produces 1,25(OH)2D3 which in turn influences hepatic growth.…”

Section: Introductionmentioning

confidence: 99%

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Lack of Production and Growth-Modulating Effects of 1α,25-Dihydroxyvitamin D<sub>3</sub> in Cultured Fetal Rat Hepatocytes

Partyka

Gelardi²,

Fadden³

et al. 1995

Neonatology

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1α,25-Dihydroxyvitamin D₃ [1,25(OH)₂D₃], the hormonal form of vitamin D₃, has been shown to play a role in the regulation of growth of the regenerating adult rat liver following partial hepatectomy. In addition, a recent study implicated the neonatal liver as a possible extrarenal site of 1,25(OH)₂D₃ synthesis. Therefore, in our present study we used rapidly growing fetal hepatocytes in culture as a model cell line for regenerating hepatocytes and tested the hypothesis that fetal hepatocytes locally produce 1,25(OH)₂D₃ which in turn regulates their growth. Hepatocytes isolated from 19-day rat fetuses were grown in culture for 24 h in minimal essential medium without added serum or mitogens. To identify 1,25(OH)₂D₃ production, we incubated fetal hepatocytes in culture with ³H-25-hydroxyvitamin D₃ (³H-25-OH D₃) for 2,6 and 24 h. High-pressure liquid chromatographic analysis of the lipid extract of the medium and cells revealed no evidence of conversion of ³H-25-OH D₃ into ³H-1,25(OH)₂D₃. Additionally, to investigate the effect of 1,25(OH)₂D₃ on DNA synthesis in fetal liver, we measured ³H-thymidine incorporation by the cultured fetal hepatocytes following 24 h of exposure to various concentrations of 1,25(OH)₂D₃. The results of DNA synthesis revealed no effect of 1,25(OH)₂D₃ on fetal hepatocyte growth. As alterations in growth regulation by 1,25(OH)₂D₃ in other cells are thought to be mediated by intracellular vitamin D receptors (VDR), the expression of the VDR message in the fetal and maternal tissues of a pregnant rat was studied. RNA was first isolated from fetal liver, fetal kidney, maternal liver and maternal kidney, and the corresponding cDNA was then generated by reverse transcription. The cDNA for VDR was amplified by PCR using oligonucleotide primers specific for the rat VDR sequence. A minor PCR product DNA for VDR in fetal liver was detected compared to the level of expression in fetal kidney and maternal liver and kidney. The low level of VDR expression in fetal liver may explain the lack of sensitivity of fetal hepatocyte DNA synthesis to 1,25(OH)₂D₃. In summary, our data suggest that in the fetal rat liver, 1,25(OH)₂D₃ is not locally produced and does not modulate DNA synthesis.

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Section: Resultscontrasting

confidence: 56%

Section: Introductionmentioning

confidence: 99%

Lack of Production and Growth-Modulating Effects of 1α,25-Dihydroxyvitamin D<sub>3</sub> in Cultured Fetal Rat Hepatocytes

Partyka

Gelardi²,

Fadden³

et al. 1995

Neonatology

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“…Sacrifice was 3 h after the last dose. Kidneys were perfused with cold 0.25 M sucrose in phosphate-buffered saline, pH 7.4, pooled from four mice, homogenized, and precipitates were prepared as described previously (21); incubations (0.5 ml; 12 mg/ml protein) with 50 M 25-(OH)D 3 were for 1 h at 37°C (21). Purification and quantitation of generated 24,25-(OH) 2 D 3 were by solid phase extraction and HPLC (21).…”

Section: Methodsmentioning

confidence: 99%

Retinoid X Receptor Acts as a Hormone Receptor in Vivo to Induce a Key Metabolic Enzyme for 1,25-Dihydroxyvitamin D3

Allegretto¹,

Shevde²,

Zou³

et al. 1995

Journal of Biological Chemistry

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We demonstrate here that RNA levels of 25-hydroxyvitamin D 3 -24-hydroxylase (24-(OH)ase), a key catabolic enzyme for 1,25-dihydroxyvitamin D 3 , are increased by a highly selective retinoid X receptor (RXR) ligand, LG100268, in mice within hours. Correspondingly, upon LG100268 treatment, kidney 24-(OH)ase enzymatic activity increases 5-10-fold. The endogenous retinoid hormones, all-trans-retinoic acid and 9-cis-retinoic acid, and the synthetic retinoic acid receptor-selective compound, TTNPB, also stimulate 24-(OH)ase. Additionally, we show that LG100268 stimulates transcription of a luciferase reporter plasmid driven by 24-(OH)ase promoter sequences in the presence of RXR in CV-1 cell cotransactivation assays. This first demonstration of a gene that is regulated in the intact animal through an RXR-mediated pathway confirms earlier hypotheses that RXR is a bona fide hormone receptor. Regulation of a key gene in the vitamin D signaling pathway by a retinoid transducer may provide a molecular basis for some of the documented biological effects of vitamin A on bone and vitamin D metabolism. Retinoic acid receptors (RARs)1 have been shown to act as hormone receptors by virtue of the fact that they bind all-transretinoic acid (tRA) with high affinity and activate target genes in the presence of tRA in cell-based cotransactivation assays and in vivo (reviewed in Ref. 1). Retinoid X receptors (RXRs) are also thought to act as hormone receptors (reviewed in Ref. 1) since they bind 9-cis-retinoic acid (9cRA) with high affinity (2, 3) and have been shown to stimulate transcription from distinct elements known as RXR-responsive elements in promoter sequences of the apolipoprotein A1 (apoA1) and cellular retinol-binding protein II (CRBPII) genes in cell-based cotransactivation assays in response to 9cRA (2, 3), tRA (4, 5), or RXR-selective ligands (6, 7). However, these genes have not been shown to be regulated by retinoids in vivo. While another gene product (growth hormone) has been shown to increase in cultured cells treated with RXR-and RAR-selective ligands (8), there are currently no known biological target genes of RXR in the intact animal.RXRs are thought to form homodimers upon interaction with ligand (1) to activate putative RXR-selective genes, such as CRBPII and apoA1, through RXR-responsive elements in the promoters of those genes (2-7). RXR is also known to participate in heterodimers with a number of other intracellular receptors, including the vitamin D receptor (VDR), RAR, or thyroid hormone receptor to activate a variety of target genes, which are stimulated by 1,25-dihydroxyvitamin D 3 (1,25-(OH) 2 D 3 ), tRA, or thyroid hormone, respectively (1). RXR is thought to act as a silent partner in these interactions, although the effects of liganding of RXR under these circumstances have not been thoroughly explored. Additionally, recent studies describe instances of stimulation of gene transcription by hormone-occupied RXR interacting with a supposedly unoccupied orphan receptor (9, 10).To study the consequen...

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“…The liver, well known to be the major site for 25OHD production, has also been shown to express CYP27b1 [68], which at least in the rat appears to disappear postnatally [69]. This observation has received little further investigation following these initial and early publications.…”

Section: Tissue Distribution Of Cyp27b1mentioning

confidence: 89%

Extra Renal Synthesis of 1,25-dihydroxyvitamin D and its Health Implications

Bikle

2009

Clinic Rev Bone Miner Metab

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Although the kidney was initially thought to be the sole organ responsible for the production of 1,25(OH) 2 D 3 via its enzyme CYP27b1, it is now appreciated that the expression of CYP27b1 in tissues other than the kidney is wide spread. However, the kidney is the major source for circulating 1,25(OH) 2 D 3 . Therefore the existence of the capacity for extra renal 1,25(OH) 2 D 3 production begs the question why, and in particular whether the extra renal production of 1,25(OH) 2 D 3 has physiologic importance. In this chapter this question will be discussed. First a compilation of the extra renal sites for CYP27b1 expression is provided. This is followed by a discussion of the regulation of CYP27b1 expression and activity in extra renal tissues, pointing out that such regulation is tissue specific and different from that of CYP27b1 in the kidney. Finally the physiologic significance of extra renal 1,25(OH) 2 D 3 production is examined, with special focus on the role of CYP27b1 in regulation of cellular proliferation and differentiation, hormone secretion, and immune function. At this point the data do not clearly demonstrate an essential role for CYP27b1 expression in any tissue outside the kidney, but several examples pointing in this direction are provided. With the availability of the mouse enabling tissue-specific deletion of CYP27b1, the role of extra renal CYP27b1 expression can now be addressed definitively.

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25-Hydroxyvitamin D3-1 alpha-hydroxylase in porcine hepatic tissue: subcellular localization to both mitochondria and microsomes.

Cited by 34 publications

References 46 publications

Lack of Production and Growth-Modulating Effects of 1α,25-Dihydroxyvitamin D<sub>3</sub> in Cultured Fetal Rat Hepatocytes

Lack of Production and Growth-Modulating Effects of 1α,25-Dihydroxyvitamin D<sub>3</sub> in Cultured Fetal Rat Hepatocytes

Retinoid X Receptor Acts as a Hormone Receptor in Vivo to Induce a Key Metabolic Enzyme for 1,25-Dihydroxyvitamin D3

Extra Renal Synthesis of 1,25-dihydroxyvitamin D and its Health Implications

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