Altered hepatic function in vitamin D-deprived rats

Pahuja, D.N.; Deshpande, U. R.; Soman, C. S.; Nadkarni, G.D.

doi:10.1016/0168-8278(89)90053-6

Cited by 4 publications

(3 citation statements)

References 24 publications

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“…The hormone 1,25(OH) 2 D 3 , either directly or through its calcaemic effects, also has effects on liver in the absence of the growth promotion that follows hepatectomy. Vitamin D deficiency significantly alters hepatic function (Sikorska et al 1983;Haddad et al 1987;Pahuja et al 1989). The hormone also stimulates the activity of isocitrate lyase and malate synthase, key enzymes in the glyoxylate cycle in the liver (Sikorska et al 1983;Davis et al 1990), increases the activity of the NADPH-dependent cytosolic triiodothyronine-binding protein in rat liver and in dRLh rat hepatoma-derived cells (Hashizume et al 1991) and enhances transferrin synthesis in primary cultures of rat hepatocytes (Taniguchi et al 1990).…”

Section: Discussionmentioning

confidence: 97%

Vitamin D receptor ontogenesis in rat liver

Segura

Alonso²,

Fraga³

et al. 1999

Histochemistry and Cell Biology

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Vitamin D through its receptor (VDR) plays a major role in bone mineral metabolism. However, VDR is also present in a variety of cell lines as well as in numerous tissues, suggesting other functions of the hormone beyond bone metabolism and mineral homeostasis. At the liver level, it has been shown that vitamin D induces numerous changes (i.e. enzyme activity level, stimulation of some metabolic pathways and stimulation of the normal liver recovery after partial hepatectomy). However, some works did not find VDR in the liver, and also used liver tissue as a negative control of VDR gene expression. In this paper, we examined fetal, neonatal and adult rat tissues for the presence of VDR using a sensitive RT-PCR technique and immunohistochemistry. We found VDR mRNA and VDR protein in rat liver at all different periods of rat life. Thus, we suggest that some of the actions of vitamin D on liver could be mediated at the genomic level through the VDR, and that the use of this tissue as a negative control of VDR gene expression is clearly inappropriate.

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Section: Discussionmentioning

confidence: 97%

Vitamin D receptor ontogenesis in rat liver

Segura

Alonso²,

Fraga³

et al. 1999

Histochemistry and Cell Biology

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“…Recent studies have demonstrated that hepatic tissue has several physiological responses to 1,25(OH)2D3 (16)(17)(18)(19)(20)(21)(22)(23)(24)46) and appears to contain high-affinity receptors for this potent hormone (47). General vitamin D deficiency in the rat has been shown to alter hepatic function as manifested by delayed bromosulfthalein clearance and elevated plasma transaminases (16).…”

Section: Identificationmentioning

confidence: 99%

“…Because of the important role of 1,25(OH)2D3 in various aspects of hepatic function (16)(17)(18)(19)(20)(21)(22)(23)(24), the possibility that the liver could synthesize in situ this hormonal form of vitamin D3 was investigated. It is reported here that both hepatic mitochondria and microsomes possess a 25(OH)D3 lahydroxylase in significant amounts.…”

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confidence: 99%

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

Hollis

1990

Proc. Natl. Acad. Sci. U.S.A.

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In vitro studies were performed to assess the ability of hepatic homogenates, mitochondria, and microsomes to la-hydroxylate 25-hydroxyvitamin D3 (25(OH)D3]. Addition of 25(OH)D3 to either hepatic mitochondria or microsomes caused a concentration-dependent increase in the production of 1,25-dihydroxyvitamin D3 [1,25(OH) Because of its inability to achieve substrate saturation, meaningful kinetic parameters could not be calculated for the hepatic microsomal la-hydroxylase. These data demonstrate the liver to be an even more dynamic organ than was previously believed with respect to vitamin D metabolism in that the liver has the potential to produce 1,25(OH)2D3 in situ by at least two separate mechanisms.It is well established that various side chain and/or A-ring hydroxylation reactions are essential for the metabolic activation of vitamin D3 (1, 2). Circulating vitamin D3 first undergoes a hepatic conversion to 25-hydroxyvitamin D3 [25(OH)D3] (3). The hydroxylase enzymes responsible for this conversion are known to be cytochrome P-450 mixed-function oxidases that are NADPH dependent and are located in both hepatic mitochondria (4-6) and microsomes (7,8). Final activation of 25(OH)D3 into 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] takes place primarily in the kidney (9). The renal enzyme responsible for this activation, 25(OH)D3 lahydroxylase, is also known to be a cytochrome P450 mixedfunction oxidase that is located solely in the inner mitochondrial membrane (10, 11). In recent years, other tissues have also been shown to be capable of synthesizing 1,25(OH)2D3, including placenta (12), bone cells (13), lymphatic tissue (14), and keratinocytes (15). Compared with the renal 25(OH)D3 la-hydroxylase, very little information is known with respect to the metabolic control of these extrarenal 25(OH)D3 lahydroxylases and essentially no information is available concerning their subcellular distribution.Because of the important role of 1,25(OH)2D3 in various aspects of hepatic function (16-24), the possibility that the liver could synthesize in situ this hormonal form of vitamin D3 was investigated. It is reported here that both hepatic mitochondria and microsomes possess a 25(OH)D3 lahydroxylase in significant amounts. These enzymes differ in some characteristics, but both appear to behave as cytochrome P-450 mixed-function oxidases. MN). Coomassie blue protein assay reagent was purchased from Pierce. Nicotinamide adenine dinucleotide phosphate, isocitrate, N,N'-diphenylethylenediamine (DPED), dithiothreitol, and ethylenediaminetetraacetic acid were purchased from Sigma. All solvents were of HPLC grade and were obtained from Fisher. MATERIALS AND METHODS ReagentsLivers. Livers from 3-month-old castrated male pigs, maintained on stock diet, were obtained at the time of slaughter. The livers were perfused with ice-cold 0.15 M NaCl, minced, and placed in an appropriate volume of ice-cold 50 mM Na2HPO4 (pH 7.4) buffer containing 0.25 M sucrose and 0.5 mM EDTA to provide a 20% (wt/vol) 6009The publication costs of th...

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