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1.
Stimulation of 1,25-dihydroxyvitamin D3 production by 1,25-dihydroxyvitamin D3 in the hypocalcaemic rat. 总被引:5,自引:0,他引:5
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Serum 1,25-dihydroxyvitamin D3 concentration and renal 25-hydroxyvitamin D 1 alpha-hydroxylase activity were measured in rats fed various levels of calcium, phosphorus and vitamin D3. Both calcium deprivation and phosphorus deprivation greatly increased circulating levels of 1,25-dihydroxyvitamin D3. The circulating level of 1,25-dihydroxyvitamin D3 in rats on a low-calcium diet increased with increasing doses of vitamin D3, whereas it did not change in rats on a low-phosphorus diet given increasing doses of vitamin D3. In concert with these results, the 25-hydroxyvitamin D 1 alpha-hydroxylase activity was markedly increased by vitamin D3 administration to rats on a low-calcium diet, whereas the same treatment of rats on a low-phosphorus diet had no effect and actually suppressed the 1 alpha-hydroxylase in rats fed an adequate-calcium/adequate-phosphorus diet. The administration of 1,25-dihydroxyvitamin D3 to vitamin D-deficient rats on a low-calcium diet also increased the renal 25-hydroxy-vitamin D 1 alpha-hydroxylase activity. These results demonstrate that the regulatory action of 1,25-dihydroxyvitamin D3 on the renal 25-hydroxyvitamin D3 1 alpha-hydroxylase is complex and not simply a suppressant of this system. 相似文献
2.
Besides its role in regulating serum levels of calcium and phosphorus, 1alpha, 25-dihydroxyvitamin D3 (1,25-(OH)2D3) has potent effects on the immune system and suppresses disease in several animal models of autoimmune disorders including experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis. While the amount of 1,25-(OH)2D3 needed to prevent EAE is dependent on the gender of the mouse and amount of calcium available in the diet, the minimum levels of 1,25-(OH)2D3 sufficient to prevent disease cause hypercalcemia. To test if hypercalcemia independent of high levels of 1,25-(OH)2D3 can suppress EAE, we used a 25-hydroxyvitamin D3-1alpha-hydroxylase (1alpha-hydroxylase) knockout mouse strain. Because these 1alpha-hydroxylase knockout mice lack the parathyroid hormone (PTH)-regulated enzyme that synthesizes 1,25-(OH)2D3, hypercalcemia from increased bone turnover was created by continuous administration of PTH without changing the circulating levels of 1,25-(OH)2D3. This PTH-mediated hypercalcemia generated after EAE induction prevented disease in female mice but not male mice. When hypercalcemia was prevented by diet manipulation, PTH administration no longer prevented EAE. We conclude that hypercalcemia is able to prevent EAE after disease induction in female mice. 相似文献
3.
Metabolism of 25-hydroxyvitamin D3 in renal slices from the X-linked hypophosphatemic (Hyp) mouse: abnormal response to fall in serum calcium 总被引:2,自引:0,他引:2
H S Tenenhouse 《Cell calcium》1984,5(1):43-55
The effect of the X-linked Hyp mutation on 25-hydroxyvitamin D3 (25-OH-D3) metabolism in mouse renal cortical slices was investigated. Vitamin D replete normal mice and Hyp littermates fed the control diet synthesized primarily 24,25-dihydroxyvitamin D3 (24,25-(OH)2D3); only minimal synthesis of 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) was detected in both genotypes and 1,25-(OH)2D3 formation was not significantly greater in Hyp mice relative to normal littermates, despite hypophosphatemia and hypocalcemia in the mutants. Calcium-deficient diet fed to normal mice reduced serum calcium (p less than 0.01), increased renal 25-hydroxyvitamin D3-1-hydroxylase (1-OHase) activity (p less than 0.05), and decreased 25-hydroxyvitamin D3-24-hydroxylase (24-OHase) activity (p less than 0.05). In contrast, Hyp littermates on the calcium-deficient diet had decreased serum calcium (p less than 0.01), without significant changes in the renal metabolism of 25-OH-D3. Both normal and Hyp mice responded to the vitamin D-deficient diet with a fall in serum calcium (p less than 0.01), significantly increased renal 1-OHase, and significantly decreased renal 24-OHase activities. In Hyp mice, the fall in serum calcium on the vitamin D-deficient diet was significantly greater than that observed on the calcium-deficient diet. Therefore the ability of Hyp mice to increase renal 1-OHase activity when fed the vitamin D-deficient diet and their failure to do so on the calcium-deficient diet may be related to the resulting degree of hypocalcemia. The results suggest that although Hyp mice can respond to a disturbance of calcium homeostasis, the in vivo signal for the stimulation of renal 1-OHase activity may be set at a different threshold in the Hyp mouse; i.e. a lower serum calcium concentration is necessary for Hyp mice to initiate increased synthesis of 1,25(-OH)2D3. 相似文献
4.
Evidence for calcium-dependent control of 1,25-dihydroxyvitamin D3 production by rat kidney proximal tubules 总被引:4,自引:0,他引:4
The role of calcium in the parathyroid hormone-mediated increase in 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) production was evaluated using isolated proximal tubules from rats fed a low calcium diet (0.002% Ca) for 14 days. Tubules were prepared by collagenase digestion and centrifugation through Percoll. Tubules from rats fed a low calcium diet produced 1,25-(OH)2D3 at rates 10 times that of tubules from rats fed normal calcium diet (1.2% Ca). In vitro 1,25-(OH)2D3 biosynthesis was highly dependent upon extracellular calcium with inhibition in the absence of medium calcium and maximal production at 0.25 mM medium calcium (0.9 +/- 0.25 versus 15.1 +/- 2.3 nmol/mg protein/5 min, p less than 0.03). Inhibition of 1,25-(OH)2D3 production was partly due to depressed ATP content (0 versus 1.2 mM calcium, 6.8 +/- 0.6 versus 12.7 +/- 0.6 nmol/mg protein, p less than 0.006). EGTA reduced 1,25-(OH)2D3 synthesis and total cell calcium and ATP production. Ruthenium red blocked the inhibitory effects of EGTA on 1,25-(OH)2D3 production. Barium (1.0 mM) inhibited 1,25-(OH)2D3 production (7.2 +/- 0.5 versus 3.4 +/- 0.3, p less than 0.001) without altering ATP production. The calcium ionophore A23187 increased 1,25-(OH)2D3 production in a calcium-dependent manner. It is concluded that parathyroid hormone-mediated increases in 1,25-(OH)2D3 production, as during low calcium diet, require extracellular calcium. Extracellular calcium maintains mitochondrial calcium at optimal concentrations for normal ATP production, a requirement for 25-hydroxyvitamin D3-1-hydroxylase (25-OH-D3-1-hydroxylase) activity. Inhibition of 25-OH-D3-1-hydroxylase activity by barium without an alteration of ATP suggests calcium may also control 1,25-(OH)2D3 production independent of its effects on oxidative phosphorylation, perhaps through a direct interaction with one or more components of the 25-OH-D3-1-hydroxylase. 相似文献
5.
Xie Z Munson SJ Huang N Portale AA Miller WL Bikle DD 《The Journal of biological chemistry》2002,277(40):36987-36990
The synthesis of 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) from its precursor, 25-dihydroxyvitamin D(3) (25(OH)D(3)), is catalyzed by the mitochondrial cytochrome P450 enzyme 25-hydroxyvitamin D(3)-1alpha-hydroxylase (1alpha-hydroxylase). It has been generally assumed that 1,25(OH)(2)D(3) inhibits the activity of this enzyme by regulating its expression at the genomic level. We confirmed that 1,25(OH)(2)D(3) reduced the apparent conversion of 25(OH)D(3) to 1,25(OH)(2)D(3) while stimulating the conversion of 1,25(OH)(2)D(3) and 25(OH)D(3) to 1,24,25(OH)(3)D(3) and 24,25(OH)(2)D(3), respectively. However, 1,25(OH)(2)D(3) failed to reduce the abundance of its mRNA or its encoded protein in human keratinocytes. Instead, when catabolism of 1,25(OH)(2)D(3) was blocked with a specific inhibitor of the 25-hydroxyvitamin D(3)-24-hydroxylase (24-hydroxylase) all apparent inhibition of 1alpha-hydroxylase activity by 1,25(OH)(2)D(3) was reversed. Thus, the apparent reduction in 1alpha-hydroxylase activity induced by 1,25(OH)(2)D(3) is due to increased catabolism of both substrate and product by the 24-hydroxylase. We believe this to be a unique mechanism for autoregulation of steroid hormone synthesis. 相似文献
6.
Dardenne O Prud'homme J Glorieux FH St-Arnaud R 《The Journal of steroid biochemistry and molecular biology》2004,(1-5):327-330
The treatment of choice for pseudo Vitamin D deficiency rickets (PDDR), caused by mutations in the 25-hydroxyvitamin D-1alpha-hydroxylase (CYP27B1; 1alpha-OHase) gene, is replacement therapy with 1,25(OH)(2)D(3). We have previously engineered an animal model of PDDR by targeted inactivation of the 1alpha-OHase gene in mice (Endocrinology 142 (2001) 3135). Replacement therapy was performed in this model, and compared to feeding with a high calcium diet containing 2% calcium, 1.25% phosphorus, 20% lactose (rescue diet). Blood biochemistry analysis revealed that both rescue treatments corrected the hypocalcemia and secondary hyperparathyroidism. Bone histology and histomorphometry confirmed that the rickets and osteomalacia were cured by both rescue protocols. However, despite the restoration of normocalcemia, the rescue diet did not entirely correct bone growth as femur size remained significantly smaller than control in 1alpha-OHase(-/-) mice fed the rescue diet. These results demonstrate that correction of the abnormal mineral ion homeostasis by feeding with a high calcium rescue diet is effective to rescue the PDDR phenotype of 1alpha-OHase mutant mice. This treatment, however, does not appear as effective as 1,25(OH)(2)D(3) replacement therapy since bone growth remained impaired. 相似文献
7.
The renal 25-hydroxyvitamin D-3-1 alpha-hydroxylase (1 alpha-hydroxylase) activity and circulating levels of 1,25-dihydroxyvitamin D (1,25(OH)2D) were measured in pregnant guinea-pigs and their offspring. Serum levels of 1,25(OH)2D were significantly elevated in pregnant guinea-pigs but the renal enzyme activity was not different from non-pregnant animals. The fetal renal 1 alpha-hydroxylase activity was about 6-fold higher than the maternal level, whereas circulating 1,25(OH)2D was low. Treatment with pharmacological doses of 1,25(OH)2D3 increased circulating 1,25(OH)2D and depressed the renal 1 alpha-hydroxylases both in the mother and the fetus. In newborn guinea-pigs the enzyme activity was up to 10-times that seen in adults. It declined over the first 3 weeks, showing no difference between the sexes. In sexually mature animals the males had a significantly higher 1 alpha-hydroxylase activity than the female. However, this higher enzyme activity was not correlated to serum testosterone. Around the time the animals reached sexual maturity serum 1,25(OH)2D increased in both sexes. In the males this rise was correlated to an increase in serum testosterone. It is concluded that the maternal renal 1 alpha-hydroxylase activity is unchange in late pregnancy, compared to non-pregnant females. The data indicate that the fetus produces 1,25(OH)2D, and may contribute to the maternal circulating 1,25(OH)2D. The sex difference in 1 alpha-hydroxylase activity previously demonstrated is manifest at about the time of puberty. 相似文献
8.
M Nakada Y Tanaka H F DeLuca Y Kobayashi N Ikekawa 《Archives of biochemistry and biophysics》1985,241(1):173-178
23,23-Difluoro-25-hydroxyvitamin D3 is 5-10 times less active than 25-hydroxyvitamin D3 in stimulating intestinal calcium transport, bone calcium mobilization, increasing serum phosphorus, mineralization of rachitic bone, and binding to the plasma transport protein in rats. It is converted to 23,23-difluoro-1 alpha, 25-dihydroxyvitamin D3 by chick renal 25-hydroxyvitamin D-1-hydroxylase. This compound is one-seventh as active as 1,25-dihydroxyvitamin D3 in binding to the chick intestinal receptor for 1,25-dihydroxyvitamin D3. Thus, fluoro substitution on carbon-23 of vitamin D has an unexpected and unexplained suppressive action on plasma binding and biological activity. However, since this substitution does not block the biological response of 25-hydroxyvitamin D3, these results provide additional evidence that 23-hydroxylation of vitamin D is not involved in biological function. 相似文献
9.
Twenty-four young pigs were divided into three groups and each fed a replete, low calcium (Ca) or low phosphorus (P) diet. It was found that the deficient diets induced rises in renal 25 hydroxy-vitamin D 1,hydroxylase (1-hydroxylase) activity, circulating 1,25 dihydroxy-vitamin D3 (1,25 (OH)2-D3) and Ca binding protein (CaBP) and intestinal 1,25(OH)2D3 and CaBP. All these rises were statistically significant in the low Ca group but only the rises in the 1-hydroxylase activity and intestinal 1,25(OH)2D3 were significant in the low P group. A high degree of correlation existed between the parameters. There was no enhancement of intestinal 1,25(OH)2D3 or CaBP concentration relative to the 1-hydroxylase activity in the low P pigs as occurs in the chick. The low-P-induced rise in 1-hydroxylase activity was independent of parathyroid hormone. 相似文献
10.
On the regulatory importance of 1,25-dihydroxyvitamin D3 and dietary calcium on serum levels of 25-hydroxyvitamin D3 in rats 总被引:1,自引:0,他引:1
The serum level of 25-hydroxyvitamin D3 in rats was found to vary with the dietary intake of calcium. An increase in the dietary intake of calcium was found to be associated with an increase in the concentration of 25-hydroxyvitamin D3 and a decrease in the concentration of 1,25-dihydroxyvitamin D in serum. Intraperitoneal administration of 1,25-dihydroxyvitamin D3 was found to depress the serum concentration of 25-hydroxyvitamin D3 in rats on both medium and high calcium diets. These changes in the serum levels of 25-hydroxyvitamin D3 were not associated with statistically significant changes in the activity of mitochondrial vitamin D3 25-hydroxylase in the liver. Possible mechanisms for the regulation of the level of circulating 25-hydroxyvitamin D3 in serum are discussed. 相似文献
11.
12.
Panda DK Miao D Bolivar I Li J Huo R Hendy GN Goltzman D 《The Journal of biological chemistry》2004,279(16):16754-16766
We employed a genetic approach to determine whether deficiency of 1,25-dihydroxyvitamin D (1,25(OH)2D) and deficiency of the vitamin D receptor (VDR) produce the same alterations in skeletal and calcium homeostasis and whether calcium can subserve the skeletal functions of 1,25(OH)2D and the VDR. Mice with targeted deletion of the 25-hydroxyvitamin D 1alpha-hydroxylase (1alpha(OH)ase-/-) gene, the VDR gene, and both genes were exposed to 1) a high calcium intake, which maintained fertility but left mice hypocalcemic; 2) this intake plus three times weekly injections of 1,25(OH)2D3, which normalized calcium in the 1alpha(OH)ase-/- mice only; or 3) a "rescue" diet, which normalized calcium in all mutants. These regimens induced different phenotypic changes, thereby disclosing selective modulation by calcium and the vitamin D system. Parathyroid gland size and the development of the cartilaginous growth plate were each regulated by calcium and by 1,25(OH)2D3 but independent of the VDR. Parathyroid hormone secretion and mineralization of bone reflected ambient calcium levels rather than the 1,25(OH)2D/VDR system. In contrast, increased calcium absorption and optimal osteoblastogenesis and osteoclastogenesis were modulated by the 1,25(OH)2D/VDR system. These studies indicate that the calcium ion and the 1,25(OH)2D/VDR system exert discrete effects on skeletal and calcium homeostasis, which may occur coordinately or independently. 相似文献
13.
Li J Byrne ME Chang E Jiang Y Donkin SS Buhman KK Burgess JR Teegarden D 《The Journal of steroid biochemistry and molecular biology》2008,112(1-3):122-126
High vitamin D intake is associated with reduced insulin resistance. Expression of extra-renal 1alpha,25-dihydroxyvitamin D hydroxylase (1alpha-hydroxylase) has been reported in several tissues and contributes to local synthesis of 1alpha,25-dihydroxyvitamin D(3) (1,25(OH)(2)D) from the substrate 25-hydroxyvitamin D (25OHD). Expression and dietary regulation of 1alpha-hydroxylase in tissues associated with energy metabolism, including adipose tissue, has not been assessed. Male Wistar rats were fed a high calcium (1.5%) and high vitamin D (10,000IU/kg) or a low calcium (0.25%), low vitamin D (400IU/kg) with either a high fat (40% energy) or high sucrose (66% energy) dietary background for 14 weeks. Expression of 1alpha-hydroxylase, assessed by real time PCR, was detected in adipose tissue and did not differ with dietary level of calcium and vitamin D. 1alpha-Hydroxylase mRNA was also detected in 3T3-L1 preadipocytes and 25OHD treatment at 10nM levels induced 1,25(OH)(2)D responsive gene, CYP24, and this response was reduced in the presence of the p450 inhibitor, ketoconazole. In addition, (3)H 25OHD was converted to (3)H 1,25(OH)(2)D in intact 3T3-L1 preadipocytes. Cumulatively, these results demonstrate that 1alpha-hydroxylase is expressed in adipose tissue and is functional in cultured adipocytes. Thus, the capacity for local production may play a role in regulating adipocyte growth and metabolism. 相似文献
14.
A single 325-pmol dose of 1,25-dihydroxyvitamin D3 given to chicks fed a vitamin D-deficient diet containing 3% calcium and 0.6% phosphorus suppresses renal mitochondrial 25-hydroxyvitamin D3-1α-hydroxylase and stimulates the 25-hydroxyvitamin D3-24-hydroxylase as measured by in vitro assay. This alteration in the enzymatic activity takes place over a period of hours. The administration of parathyroid hormone rapidly suppresses the 25-hydroxyvitamin D3-24-hydroxylase. The alterations in the hydroxylases by parathyroid hormone or 1,25-dihydroxyvitamin D3 are not related to changes in serum clacium or phosphate but could be related to changes in intracellular levels of these ions. Actinomycin D or cycloheximide given in vivo reduces the 25-hydroxyvitamin D3-24-hydroxylase activity rapidly which suggests that the turnover of the enzyme and its messenger RNA is rapid (1- and 5-h half-life, respectively). The half-lives of the hydroxylases are sufficiently short to permit a consideration that the regulation by 1,25-dihydroxyvitamin D3 and parathyroid hormone may involve enzyme synthesis and degradation. 相似文献
15.
We have shown previously that the in vitro activity of the renal vitamin K-dependent gamma-glutamyl carboxylase toward synthetic oligopeptide substrates is stimulated by administration of either parathyroid hormone (PTH) or 1,25-dihydroxycholecalciferol [1,25(OH)2D3] to rats [(1983) J. Biol. Chem. 258, 12783-12786]. Here we report that administration of 1,25(OH)2D3 to rats increases their levels of endogenous carboxylase substrate as well. Rats fed a vitamin D-deficient diet had highly elevated serum PTH levels while vitamin D-replete animals had undetectable levels. Furthermore, since PTH increases 1,25(OH)2D3 levels by stimulating renal 25-hydroxyvitamin D-1 alpha-hydroxylase, it is very likely that the stimulatory effects of PTH on the renal vitamin K-dependent carboxylating system are mediated by 1,25(OH)2D3. 相似文献
16.
The endocrine hormone, 1alpha,25-dihydroxyvitamin D(3) (1,25D) is an important regulator of calcium and phosphorus homeostasis. In this context, 1,25D is generally recognized as necessary for the maintenance of a healthy skeleton through its actions on the small intestine. In this review, we highlight the direct effects of 1,25D on the constituent cells of the bone, actions that are independent of effects on the intestine and kidney. We also consider the evidence that 25D levels, not 1,25D levels, correlate best with parameters of bone health, and that the bone itself is a site of metabolic conversion of 25D into 1,25D, by virtue of its expression of the 25-hydroxyvitamin D 1alpha-hydroxylase, CYP27B1. We review the evidence that at least osteoblasts and chondrocytes, and possibly also bone resorbing osteoclasts, are capable of such metabolic conversion, and therefore that these cells likely participate in autocrine and paracrine loops of vitamin D metabolism. We conclude that the skeleton is an intracrine organ for vitamin D metabolism, challenging the long-held notion that 1,25D is solely an endocrine hormone. 相似文献
17.
S K Paulson H F DeLuca F Battaglia 《Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N.Y.)》1987,185(3):267-271
The plasma concentrations of calcium; inorganic phosphorus; 25-hydroxyvitamin D; 24,25-dihydroxyvitamin D; and 1,25-dihydroxyvitamin D were determined in sheep maternal and fetal arterial circulations. In addition, plasma concentrations of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D were determined simultaneously across the uterine and umbilical circulations. Fetal arterial levels of calcium (r = 0.560); inorganic phosphorus (r = -0.095); and 1,25-dihydroxyvitamin D (r = 0.040) were significantly higher than and did not correlate with maternal arterial levels. Maternal levels of 25-hydroxyvitamin D were significantly higher than and correlated (r = 0.693) with fetal 25-hydroxyvitamin D levels. No significant difference existed between maternal and fetal arterial levels of 24,25-dihydroxyvitamin D. No significant difference was detected in the concentrations of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D across the uterine or umbilical circulations. 相似文献
18.
Riggs BL 《Journal of cellular biochemistry》2003,88(2):209-215
Impaired calcium absorption and impaired adaptation to a low calcium diet are common features of aging in women and these processes are even more severely impaired in patients with osteoporotic fractures. The calcium absorption defects are associated with several abnormalities of the vitamin D-endocrine system including secondary hyperparathyroidism, intestinal resistance to 1,25-dihydroxyvitamin D (1,25(OH)(2)D) action, decreased 1,25(OH)(2)D production due to impaired 25(OH)D 1alpha-hydroxylase activity, and, in some elderly persons, nutritional deficiency of vitamin D. However, in postmenopausal women, most of these abnormalities are normalized by administration of physiologic replacement dosages of estrogen and, thus, appear to be secondary consequences of estrogen deficiency. Nonetheless, a minority of them, especially nutritional vitamin D deficiency and impaired 25(OH)D 1alpha-hydroxylase activity late in life, appear to be primary and are independent of estrogen deficiency. 相似文献
19.
Klotho, a gene related to a syndrome resembling human premature aging, functions in a negative regulatory circuit of vitamin D endocrine system 总被引:13,自引:0,他引:13
Tsujikawa H Kurotaki Y Fujimori T Fukuda K Nabeshima Y 《Molecular endocrinology (Baltimore, Md.)》2003,17(12):2393-2403
The klotho gene encodes a novel type I membrane protein of beta-glycosidase family and is expressed principally in distal tubule cells of the kidney and choroid plexus in the brain. These mutants displayed abnormal calcium and phosphorus homeostasis together with increased serum 1,25-(OH)2D. In kl-/- mice at the age of 3 wk, elevated levels of serum calcium (10.9 +/- 0.31 mg/dl vs. 10.0 +/- 0.048 mg/dl in wild-type mice), phosphorus (14.7 +/- 1.1 mg/dl vs. 9.7 +/- 1.5 mg/dl in wild type) and most notably, 1,25-(OH)2D (403 +/- 99.7 mg/dl vs. 88.0 +/- 34.0 mg/dl in wild type) were observed.Reduction of serum 1,25-(OH)2D concentrations by dietary restriction resulted in alleviation of most of the phenotypes, suggesting that they are downstream events resulting from elevated 1,25-(OH)2D. We searched for the signals that lead to up-regulation of vitamin D activating enzymes. We examined the response of 1alpha-hydroxylase gene expression to calcium regulating hormones, such as PTH, calcitonin, and 1,25-(OH)2D3. These pathways were intact in klotho null mutant mice, suggesting the existence of alternate regulatory circuits. We also found that the administration of 1,25-(OH)2D3 induced the expression of klotho in the kidney. These observations suggest that klotho may participate in a negative regulatory circuit of the vitamin D endocrine system, through the regulation of 1alpha-hydroxylase gene expression. 相似文献
20.
The existence of 25-hydroxyvitamin D3-1 alpha-hydroxylase in the liver of carp and bastard halibut. 总被引:1,自引:0,他引:1
We have found that carp and bastard halibut contain 25-hydroxyvitamin D3 (25-D3)-1 alpha-hydroxylase in the liver besides in the kidney by the following in vivo and in vitro experiments. When [3H]-25-D3 was intraperitoneally injected to vitamin D(D)-deficient carp and normal bastard halibut (D-deficient bastard halibut could not be raised because they died during farming), the profiles of high-performance liquid chromatography (HPLC) of the plasma lipid extract showed the formation of a peak corresponding to [3H]-1 alpha,25-dihydroxyvitamin D3 (1,25-D3). When [3H]-25-D3 was incubated with liver homogenates of the fish, a peak corresponding to [3H]-1,25-D3 was also observed in the profile of HPLC. The formation of the metabolite was confirmed by the thermal isomerization into the pre-isomer and mass fragmentography. Although the 1 alpha-hydroxylase was also observed in the kidney, the activity of the enzyme was lower than that in the liver. The results suggest that 25-D3-1 alpha-hydroxylase exists in the liver of carp and bastard halibut and the 25-D3 formed from D3 in the liver is immediately metabolized into 1,25-D3 in the same tissue. The suggestion is supported by the fact that D3 is a major circulating compound with small amounts of 1,25-D3 in the fish while the plasma levels of 25-D3 are under the limit of detection. 相似文献