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Biomedical subjects

I N Sergeev

Publications and source records attributed to I N Sergeev.

At least 19 recordsLinked to original sources
PubMed2004

Calcium as a mediator of 1,25-dihydroxyvitamin D3-induced apoptosis.

Cellular calcium has been implicated in induction of apoptosis. We have shown that 1,25(OH)(2)D(3)-induced apoptosis is associated with a sustained increase in concentration of intracellular Ca(2+) ([Ca(2+)](i)) resulting from depletion of the endoplasmic reticulum (ER) Ca(2+) stores and activation of the voltage-insensitive Ca(2+) entry pathway [1,25-Dihydroxyvitamin D(3), intracellular Ca(2+) and apoptosis in breast cancer cells, in: A.W. Norman, R. Bouillon, M. Thomasset (Eds.), Vitamin D: Chemistry, Biology and Clinical Applications of the Steroid Hormone, University of California, Riverside, 1997, pp. 473-474; Vitamin D and intracellular calcium, in: P. Quinn, V. Kagan (Eds.), Subcellular Biochemistry: Fat-Soluble Vitamins, Plenum Press, New York, 1998, pp. 271-297; 1,25-Dihydroxyvitamin D(3) and calcium signaling, in: A.W. Norman, R. Bouillon, M. Thomasset (Eds.), Vitamin D Endocrine System: Structural, Biological, Genetic and Clinical Aspects, University of California, Riverside, 2000, pp. 715-718; 1,25-Dihydroxyvitamin D(3) triggers calcium-mediated apoptosis in breast cancer cells, in: A.W. Norman, R. Bouillon, M. Thomasset (Eds.), Vitamin D Endocrine System: Structural, Biological, Genetic and Clinical Aspects, University of California, Riverside, 2000, pp. 399-402; Endocrine 9 (1998) 321]. This study was undertaken to investigate mechanism of 1,25(OH)(2)D(3)-induced apoptosis in breast cancer cells and compare effects of the hormone on Ca(2+) and apoptosis in cancer and normal human mammary epithelial cells. The treatment of MCF-7 breast cancer cells with 1,25(OH)(2)D(3) induced a sustained increase in [Ca(2+)](i) and activated the Ca(2+)-dependent proapoptotic proteases, micro-calpain and caspase-12, as evaluated with antibodies to active (cleaved) forms of the enzymes and the calpain substrate. The selective inhibition of Ca(2+) binding sites of micro-calpain decreased apoptotic indices in the 1,25(OH)(2)D(3)-treated cells. 1,25(OH)(2)D(3) did not induce apoptosis in normal human mammary epithelial cells (HMECs), as evaluated by DNA fragmentation (TUNEL), loss of the plasma membrane asymmetry (Annexin V assay) and morphological criteria. In these cells, 1,25(OH)(2)D(3) triggered a transient Ca(2+) response, which was not accompanied by the calpain and caspase activation. HMEC, but not MCF-7 cells expressed the Ca(2+) binding protein calbindin-D(28k) and buffered Ca(2+) increases induced by a Ca(2+) ionophore ionomycin. In conclusion, we have identified the novel apoptotic pathway in breast carcinoma cells treated with 1,25(OH)(2)D(3): increase in [Ca(2+)](i) -->micro-calpain activation --> caspase-12 activation --> apoptosis. Our findings also imply that differences of Ca(2+) regulatory mechanisms in breast cancer versus normal mammary epithelial cells underlay resistance of normal cells and susceptibility of cancer cells to 1,25(OH)(2)D(3)-induced Ca(2+)-mediated apoptosis.

Apoptosis↗
PubMed1998

Regulation of intracellular calcium in human breast cancer cells.

Regulation of intracellular Ca2+ in breast cancer may be important in modulating cell proliferation, differentiation, apoptosis, and cytotoxicity, as well as contributing to mechanisms of action of anticancer agents. One of these agents, the steroid hormone 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], is intimately involved in maintaining cellular Ca2+ homeostasis. The purpose of this study was to investigate Ca2+ regulatory pathways in breast cancer cells and to determine the role of 1,25(OH)2D3 in modulating these pathways. We examined pathways for Ca2+ entry from the extracellular space and Ca2+ mobilization from intracellular stores in the estrogen-receptor negative human breast cancer cell line BT-20. Fluorescence digital video imaging and Ca2+ indicator fura-2 were employed to measure the concentration of intracellular free Ca2+ ([Ca2+]i) and Ca2+ responses at the single-cell level. We found that BT-20 breast cancer cells expressed nonselective, voltage-insensitive Ca2+ channels (VICC), as indicated by their permeability to Mn2+, response to elevated extracellular Ca2+ with an increase in [Ca2+]i, blockage by La3+ and Ni2+, and response to K+ depolarization with a slight decrease in [Ca2+]i and Ca2+ influx. There was no evidence for voltage- dependent Ca2+ channels in BT-20 cells. Endoplasmic reticulum Ca2+ stores comprised a major intracellular Ca2+ pool, as was evident after application of a Ca2+ ionophore ionomycin in nominally Ca2+-free buffer to the cells with thapsigargin-depleted Ca2+ stores. Thapsigargin depletion of Ca2+ stores did not increase influx of extracellular Ca2+, implying no significant activation of the capacitative Ca2+ entry. 1,25(OH)2D3 did not induce a rapid rise in [Ca2+]i, yet Ca2+ influx through VICC was increased. Treatment with 1,25(OH)2D3 for 4-72 h significantly increased the percentage of cells with a markedly elevated basal [Ca2+]i. Ca2+ response of those cells to thapsigargin was attenuated. Taken together, our findings show that VICC and the thapsigargin-sensitive endoplasmic reticulum Ca2+ stores are the principal pathways for Ca2+ entry and Ca2+ mobilization in the breast cancer cell line used in this study. 1,25(OH)2D3 rapidly increases Ca2+ influx through VICC and after a chronic treatment, depletes endoplasmic reticulum Ca2+ stores. Targeting of Ca2+ signaling mediated by VICC and endoplasmic reticulum Ca2+ stores may represent a novel approach to the treatment and chemoprevention of breast cancer.

Biological Transport↗
PubMed1996

Calbindins decreased after space flight.

Exposure of the body to microgravity during space flight causes a series of well-documented changes in Ca2+ metabolism, yet the cellular and molecular mechanisms leading to these changes are poorly understood. Calbindins, vitamin D-dependent Ca2+ binding proteins, are believed to have a significant role in maintaining cellular Ca2+ homeostasis. In this study, we used biochemical and immunocytochemical approaches to analyze the expression of calbindin-D28k and calbindin-D9k in kidneys, small intestine, and pancreas of rats flown for 9 d aboard the space shuttle. The effects of microgravity on calbindins in rats from space were compared with synchronous Animal Enclosure Module controls, modeled weightlessness animals (tail suspension), and their controls. Exposure to microgravity resulted in a significant and sustained decrease in calbindin-D28k content in the kidney and calbindin-D9k in the small intestine of flight animals, as measured by enzyme-linked immunosorbent assay (ELISA). Modeled weightlessness animals exhibited a similar decrease in calbindins by ELISA. Immunocytochemistry (ICC) in combination with quantitative computer image analysis was used to measure in situ the expression of calbindins in the kidney and the small intestine, and the expression of insulin in pancreas. There was a large decrease of immunoreactivity in renal distal tubular cell-associated calbindin-D28k and in intestinal absorptive cell-associated calbindin-D9k of space flight and modeled weightlessness animals compared with matched controls. No consistent difference in pancreatic insulin immunoreactivity between space flight, modeled weightlessness, and controls was observed. Regression analysis of results obtained by quantitative ICC and ELISA for space flight, modeled weightlessness animals, and their controls demonstrated a significant correlation. These findings after a short-term exposure to microgravity or modeled weightlessness suggest that a decreased expression of calbindins may contribute to the disorders of Ca2+ metabolism induced by space flight.

Animals↗
PubMed1995

1,25-Dihydroxyvitamin D3 evokes oscillations of intracellular calcium in a pancreatic beta-cell line.

The steroid hormone 1 alpha,25-dihydroxyvitamin D3 [1,25-(OH)2D3] can elicit biological responses via a nongenomic pathway that involves rapid opening of the plasma membrane Ca2+ channels. There is also evidence that 1,25-(OH)2D3 influences insulin secretion in the pancreatic beta-cell, which is primarily mediated by a rapid rise in the concentration of intracellular free Ca2+ ([Ca2+]i). We employed fluorescent digital ratiometric video imaging at the single cell level to study the effects of 1,25-(OH)2D3 on [Ca2+]i in a pancreatic beta-cell line, RINr1046-38. In RIN cells equilibrated at a steady state glucose concentration (5.5 mM), 1,25-(OH)2D3 (2-20 nM) rapidly, within 5-10 sec, increased [Ca2+]i and evoked sinusoidal [Ca2+]i oscillations with a frequency of 1.87 +/- 0.13 min-1 and an amplitude of 236 +/- 3 nM (from the initial basal level of 110 +/- 2 nM). The [Ca2+]i oscillations were acutely dependent on extracellular Ca2+, but not on extracellular glucose. Further, we investigated the mechanisms of activation by 1,25-(OH)2D3 of the Ca2+ entry pathway in the plasma membrane and analyzed the relationship between 1,25-(OH)2D3-stimulated Ca2+ entry and Ca2+ release from intracellular stores. The 1,25-(OH)2D3-evoked [Ca2+]i oscillations were mediated by nonselective Ca2+ channels, which are permeable to Mn2+ and suppressed by extracellular La3+. Blockage of voltage-dependent Ca2+ channels by nifedipine significantly decreased the amplitude of the oscillations. Depletion of intracellular Ca2+ stores with thapsigargin did not affect the 1,25-(OH)2D3-stimulated Ca2+ entry estimated by the Mn2+ entry and fura-2 fluorescence quench, which implies that the hormone directly activates nonselective Ca2+ channels. The 1,25-(OH)2D3-evoked increase in the background Ca2+ influx appears to generate [Ca2+]i oscillations by triggering Ca2+ release through the ryanodine receptor/Ca2+ release channel, but not through activation of the inositol 1,4,5-triphosphate receptor. Our findings are consistent with a role of the plasmalemmal vitamin D receptor coupled to the plasma membrane Ca2+ channels in mediating rapid effects of the hormone. We propose that the 1,25-(OH)2D3-mediated Ca2+ signaling pathway may be involved in the regulation of insulin secretion from the pancreatic beta-cell.

Animals↗
PubMed1994

Absence of calcitriol-mediated nongenomic actions in isolated intestinal cells of the damara mole-rat (Cryptomys damarensis).

Calcitriol [1,25(OH)2D3] actions on intestinal calcium transport involve genomic and nongenomic pathways. Whether nongenomic 1,25(OH)2D3-mediated actions are employed was investigated using isolated intestinal epithelial cells of naturally vitamin D-deficient underground-dwelling damara mole-rats (Cryptomys damarensis). 1,25(OH)2D3-mediated nongenomic pathways of intestinal calcium uptake, measured by opening of 1,25(OH)2D3-activated voltage-sensitive Ca2+ channels (VSCC), did not occur. Rapid (1 min) 45Ca2+ transmembrane influx in intestinal cells was not significantly increased by the addition of 1,25(OH)2D3 (at concentrations from 10(-12) to 10(-6) nM), when compared to opening of VSCC in the presence of a depolarizing (elevated K+) buffer. Furthermore, even after 30 min calcium uptake was not significantly enhanced by the hormone. These findings support earlier reports that duodenal calcium absorption is independent of vitamin D and is a highly adaptive feature of a subterranean existence.

Animals↗
PubMed1994

Vitamin D metabolism in the Damara mole-rat is altered by exposure to sunlight yet mineral metabolism is unaffected.

Vitamin D may be endogenously synthesized in the skin in the presence of sunlight or, alternatively, acquired from dietary sources. Cryptomys damarensis appear to have a naturally impoverished vitamin D status with low plasma concentrations of both 25-hydroxyvitamin D (25(OH)D; < 5 ng/ml) and 1,25-dihydroxyvitamin D (1,25(OH)2D; < 20 pg/ml). We attribute this to their underground habitat and herbivorous habits. We questioned whether these subterranean mammals could utilize sunlight-mediated pathways and therefore compared vitamin D metabolism and function when animals were (a) housed naturally (control), (b) given an oral vitamin D3 (D3) supplement (1 IU/g dry matter food eaten per day) and (c) exposed to 10 h of sunlight. Control animals exhibited a highly efficient apparent fractional absorption of both calcium (Ca) and inorganic phosphorus (Pi) (> 90%), passive mode of intestinal mineral uptake, yet tightly regulated serum ionized calcium (Ca2+). The ratio of 25(OH)D-1 alpha-hydroxylase (1-OHase) to 25(OH)D-24R-hydroxylase (24-OHase) activity in the kidney, corresponded with a state of vitamin D deficiency. Cryptomys damarensis responded to both oral D3 supplementation and sun exposure by an increase in plasma concentration of 1,25(OH)2D with a commensurate decline (P < 0.05) in 1-OHase activity, and a resulting decrease (P < 0.05) in the ratio of 1-OHase:24-OHase activity. Despite these changes, the intestinal mode of Ca uptake and plasma total Ca, Ca2+ and Pi remained unchanged with either treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Selective biological response by target organs (intestine, kidney, and bone) to 1,25-dihydroxyvitamin D3 and two analogues.

The hormonally active form of vitamin D, 1 alpha,25-dihydroxyvitamin D3 [1 alpha,25(OH)2D3] stimulates biological responses related to calcium homeostasis, cell differentiation, and immunomodulation in many target cells, including leukemic cells. Most of these responses are dependent upon 1 alpha,25(OH)2D3 interaction with a nuclear receptor protein. Structural analogues of 1 alpha,25(OH)2D3 might allow for separation of biological function, avoiding adverse calcemic effects. This report quantitates intestinal calcium absorption, bone calcium resorption, induction of intestinal and renal calcium-binding protein (CaBP), and occupancy of the intestinal and renal nuclear 1 alpha,25(OH)2D3 receptor in vitamin D-deficient chicks after a single dose of 1 alpha,25(OH)2D3, 1 alpha,25-dihydroxyvitamin-16-ene-23-yne-D3 (analogue V), or 22-[m-(dimethylhydroxymethyl)phenyl]-23,24,25,26,27- pentanor-1 alpha-hydroxy-vitamin D3 (analogue EV). The interaction of these compounds with chick intestinal nuclear 1 alpha,25(OH)2D3 receptor and chick plasma vitamin D-binding protein was determined in vitro; analogues V and EV bound 68% and 62% [1 alpha,25(OH)2D3 receptor] and 8% and 13% (vitamin D-binding protein), respectively, as well as 1 alpha,25(OH)2D3 (100%). 1 alpha,25(OH)2D3 doses (0.075-1.2 nmol) generated responses in intestinal calcium absorption, bone calcium resorption, intestinal CaBP, and renal CaBP. When analogue V (1.2-300 nmol) was administered, increases in bone calcium resorption and renal CaBP were noted. However, a significant response in intestinal calcium absorption and intestinal CaBP appeared only after a 300-nmol dose. Unoccupied nuclear 1 alpha,25(OH)2D3 receptor in the intestine and kidney was determined in vivo after doses of 1 alpha,25(OH)2D3, analogue V, or analogue EV. Doses (0.25-6.0 nmol) of 1 alpha,25(OH)2D3 and analogue EV reduced unoccupied receptor to 24% and 59% (intestine) and to 13% and 41% (kidney), respectively. Analogue V (6.0-600 nmol) decreased unoccupied receptor in the kidney. In the intestine analogue V (300-600 nmol) reduced unoccupied receptor only to 75%. These results confirm that some vitamin D analogues can generate selective biological responses and different levels of target organ receptor occupancy.

Animals↗
PubMed1993

Vitamin D receptors in a naturally vitamin D-deficient subterranean mammal, the naked mole rat (Heterocephalus glaber): biochemical characterization.

1,25-dihydroxyvitamin D3 (1,25(OH)2D3), the hormonally active metabolite of vitamin D3 interacts with its nuclear/cytosolic receptor to induce biological responses in target tissues. Naked mole rats appear to be naturally deficient in vitamin D. The questions arise whether these animals possess the 1,25(OH)2D3 receptor (VDR) and whether they are capable of responding to 1,25(OH)2D3 via receptor-mediated pathways. Various tissues (intestine, kidney, Harderian glands, and skin) were examined for the presence and biochemical characterization (as indicated by saturation, sucrose density gradient, DNA binding, and ligand-competitive analysis) of VDRs. In addition homologous upregulation of VDRs in these tissues and induction of 25-hydroxyvitamin D3-24-hydroxylase (24-OHase) in the kidney was studied as indicators of the VDR-mediated biological responses. Naked mole rats have VDRs in the intestine, kidney, and Harderian gland but not in skin. Biochemical characterization of VDRs and VDR-mediated biological responses in the intestine and kidney correspond to those found in similar target tissues of other mammals. Harderian gland VDR is at a lower concentration yet shows a markedly higher affinity and selectivity to 1,25(OH)2D3 than that of the intestine and kidney. Vitamin D3 supplementation resulted in VDR upregulation in the intestine and kidney and induced renal 24-OHase but had no effects on VDRs in Harderian glands. These data demonstrate that naked mole rats possess VDRs in intestine, kidney, and Harderian glands; these VDRs differ in their biochemical characteristics.

Animals↗
PubMed1993

Vitamin D hydroxylases and their regulation in a naturally vitamin D-deficient subterranean mammal, the naked mole rat (Heterocephalus glaber).

The vitamin D hormone 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) is generated by a series of hydroxylation steps in the liver and kidneys. We investigated whether naturally vitamin D-deficient subterranean mammals (naked mole rats, Heterocephalus glaber) employ the same enzymatic pathways, and whether these are regulated in a similar manner to that established for other mammals. Vitamin D3-25-hydroxylase in the liver and both 25-hydroxyvitamin D3-1-hydroxylase and 25-hydroxyvitamin D3-24 hydroxylase (1-OHase and 24-OHase) in the kidney were detectable in mole rats. As expected for vitamin D-deficient mammals, the 1-OHase activity predominated over the 24-OHase. After mole rats received a supraphysiological supplement of vitamin D3, 1-OHase activity was suppressed and 24-OHase activity was enhanced. Irrespective of vitamin D status, forskolin (a protein kinase A activator) and dibutyryl cyclic AMP did not alter the activity of either 1-OHase or 24-OHase. These findings suggest that the response of renal hydroxylases to parathyroid hormone was blunted. Phorbol esters, 12-O-tetradecanoylphorbol 13-acetate (TPA) and 1-oleoyl-2-acetylglycerol (OAG) (protein kinase C activators), suppressed 1-OHase activity. 24-OHase activity was induced by TPA but not by OAG. These effects were similar to those illicited by vitamin D3 supplementation but were additive in that they increased the responses shown in vitamin D-replete mole rats. These data confirm that naturally vitamin D-deficient mole rats can convert vitamin D3 to the hormone, 1,25(OH)2D3.(ABSTRACT TRUNCATED AT 250 WORDS)

25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗
PubMed1992

Vitamin K-dependent gamma-carboxylation of the 1,25-dihydroxyvitamin D3 receptor.

It has been reported that vitamin K deficiency in the rat markedly increases the 1,25-dihydroxyvitamin D3 receptor (VDR) binding to DNA and that vitamin K-dependent gamma-carboxylation of endogenous substrates of the intestinal and renal cytosol, also containing VDR, sharply reduced that binding (Sergeev, I.N., and Spirichev, V.B. (1989) Nutr. Res. 9, 725-733). In the present study we have evaluated vitamin K-dependent 14CO2 incorporation to VDR quantitated by immunoprecipitation with anti-VDR monoclonal antibodies. The results obtained strongly suggest that VDR in vitro can undergo gamma-carboxylation in the presence of vitamin K1 and that 15-25% of Glu residues in the VDR are carboxylated in vivo. Taking into account our earlier findings, it is likely that the VDR gamma-carboxylation modulates its binding to DNA.

Animals↗
PubMed1992

[The vitamin D endocrine system and bone tissue mineral metabolism in rats with adjuvant arthritis: the effect of 1,25-dihydroxyvitamin D3].

Adjuvant arthritis was induced in male rats by injecting bacillus Calmette-Guèrin in mineral oil in a hindpaw. A decrease in bone density, calcium and phosphorus content due to polyarthritis was found in the tibia of the noninjected hind leg. Arthritic rats demonstrated serum 1,25-dihydroxyvitamin D deficiency along with constant level of 25-hydroxyvitamin D. The disease caused a significant expression of 1,25-dihydroxyvitamin D3 receptors in lymphocytes. Arthritic rats were treated with 1,25-dihydroxyvitamin D3 (0.15 mg/kg/day orally) for 35 days. The treatment prevented the development of osteoporosis and a decrease of 1,25-dihydroxyvitamin D levels as well as reduced the expression of 1,25-dihydroxyvitamin D receptors in lymphocytes.

Animals↗
PubMed1991

[Effect of the treatment with oxydevit on calcium metabolism, immune status and 1,25(OH)2D3 receptors in the lymphocytes of children with glomerulonephritis].

In all the examined children with chronic glomerulonephritis (GN), peripheral blood lymphocytes had a high concentration of receptors of 1,25 (OH)2D3, a hormonal form of vitamin D. At the same time as to the healthy children, 1,25 (OH)2D3 receptors were identified only in 27%, with the concentration being lower. A large amount of 1,25 (OH)2D3 receptors may be related to the expression of the hormone in activated lymphocytes. In addition to the normalization of calcium metabolism, the treatment with oxydevit favoured the normalization of the content of IgG and T lymphocytes as well as a reduction (to normal) of the content of 0 lymphocytes regardless of the previous treatment. Partial remission was attained in 14 out of 20 GN patients. In 10 of these children, the remission lasting 1-2 years was attained for the first time. In 17 children treated with oxydevit, the incidence of acute respiratory viral infection decreased from 6-8 times to 1-2 times a year. The data obtained allowed one to ascertain the immunomodulatory capacities of oxydevit in children with chronic glomerulonephritis.

B-Lymphocytes↗
PubMed1990

Ascorbic acid effects on vitamin D hormone metabolism and binding in guinea pigs.

Ascorbic acid deficiency in guinea pigs fed a vitamin D-replete diet caused a moderate reduction of Ca level in serum and bone; 25-hydroxy-cholecalciferol or 25-hydroxyergocalciferol (25-OHD) serum concentration tended to decline; renal 25-hydroxycholecalciferol-1-hydroxylase (1-OHase) activity decreased 50%; and 25-hydroxycholecalciferol-24-hydroxylase activity increased 1.6-fold. Chromatin 1,25-dihydroxycholecalciferol [1,25-(OH)2D3] receptor concentration in the intestinal mucosa decreased 20-30%, and the percentage of occupied receptors decreased from 12-15% to 6-8%. Receptor affinity for 1,25-(OH)2D3 did not change (Kd = 0.24-0.26 nmol/L, Kd2 = 0.06-0.10 nmol/L), but the cooperativity coefficient decreased from 1.7 to 1.4. Vitamin C deficiency potentiated effects of vitamin D deprivation and impaired a restorative action of vitamin D. It was accompanied by a marked delay in the elevation of 25-OHD concentration in serum as well as decreased 1-OHase activity in kidneys and a lower concentration of occupied 1,25-(OH)2D3 receptors in the intestinal mucosa. The data demonstrate a critical role for ascorbic acid in vitamin D metabolism and binding.

25-Hydroxyvitamin D 2↗
PubMed1990

[The role of vitamin E in metabolism and reception of vitamin D].

It was found that calcium exchange disturbances under vitamin E deficiency is due to changes in the metabolism of vitamin D. In vitamin E-deficient rats the serum blood levels of hydroxyvitamin D (25-OHD) showed no significant changes, whereas the concentration of the hormonal form of 1.25-hydroxyvitamin D [1.25(OH)2D], decreased by 40%. In vitro studies showed that the 25-hydroxylase D3 activity in the livers of rats with E-avitaminosis had a tendency to decrease (by 22%), whereas that of 24-hydroxylase dropped drastically (by 52%). The serum blood levels of the parathyroid hormone (PTH) and kidney levels of cAMP under E-avitaminosis were significantly lowered. Preincubation of kidney slices with the adenylate cyclase activator, forskolin, increased the activity of 1-OHase in about the same degree as that in vitamin E-rich rats. The free radical scavenger, BHT, added to kidney slices suppressed the activity of the both enzymes; this finding testifies to the low O2-binding affinity of these monooxygenases. The content of 1.25(OH)2D3 receptors occupied in vivo in the kidneys of vitamin E-deficient rats decreased 2.5-fold; however, the binding of 1.25(OH)2D3-receptor complexes to heterologous DNA was unaffected thereby. The vitamin deficiency in vivo results in the inhibition of vitamin D metabolism in the liver and kidney concomitant with the formation of active metabolites and decreases the concentration of hormone-receptor complexes in target tissues.

Animals↗