Improved methodology for the analysis of plasma vitamin D metabolites.
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Animals↗
Biomedical subjects
R L Horst
Publications and source records attributed to R L Horst.
Self-induction of 1,25-dihydroxyvitamin D3 metabolism limits receptor occupancy and target tissue responsiveness.
Whole cell 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) receptor (VDR) binding assays, which measure VDR in the presence of the metabolic machinery of the cell, were used in conjunction with a cytosol binding assay for VDR to determine if self-induced metabolism of 1,25-(OH)2D3 limits VDR occupancy, total VDR levels, and target cell responsiveness. Treatment of cells with 0.5 nM 1,25-(OH)2[3H]D3 for 16 h results in up-regulation of total cell VDR from 82 to 170 fmol/mg protein as measured in a cytosol binding assay. Conversely, whole cell binding assays of VDR showed a 1,25-(OH)2D3-mediated apparent down-regulation of VDR from 90 to 40 fmol/mg protein. Scatchard analysis using the cytosol binding assay demonstrated that 1,25-(OH)2D3 treatment increased total cell VDR from 93 to 154 fmol/mg protein. In contrast, Scatchard analysis with the whole cell binding assay demonstrated that 1,25-(OH)2D3 treatment resulted in reduction in total cell VDR from 100 to 64 fmol/mg protein. Initial Kd estimates with the whole cell binding assay suggested that 1,25-(OH)2D3 treatment resulted in a reduction in VDR Kd from 0.6 to 6.2 nM. This apparent reduction in the affinity of VDR for 1,25-(OH)2D3 was due to degradation of free 1,25-(OH)2[3H]D3 which occurred during whole cell saturation assay. Competitive inhibitors of 1,25-(OH)2D3 metabolism were found to reverse the apparent receptor down-regulation observed in whole cell binding assays of treated cells. In addition, the presence of competitive inhibitors amplified responses of cells to 1,25-(OH)2[3H]D3 treatment as measured by an increased occupancy of VDR by 1,25-(OH)2[3H]D3 and increased up-regulation of VDR over that observed without metabolism inhibitors. These data demonstrate that self-induced target tissue deactivation of 1,25-(OH)2D3 regulates 1,25-(OH)2D3 occupancy of VDR and ultimately the biopotency of 1,25-(OH)2D3 in target cells.
Binding, Competitive↗
Comparison of receptor binding, biological activity, and in vivo tracer kinetics for 1,25-dihydroxyvitamin D3, 1,25-dihydroxyvitamin D2, and its 24 epimer.
Scatchard analyses of 1,25-dihydroxyvitamin D receptors (VDR) from chick and rat intestine, bovine thymus, pig kidney cells (LLC-PK1), and human breast cancer cells (T-47D) demonstrated that 1,25-dihydroxyvitamin D3 (1,25-D3) and 1,25-dihydroxyvitamin D2 (1,25-D2) had equal affinities for VDR. 24-Epi-1,25-dihydroxyvitamin D2 (24-epi-1,25-D2) exhibited affinities for VDR equal to that of 1,25-D2 and 1,25-D3 in most of these tissues. Scatchard analysis with 24-epi-[3H]1,25-D2 underestimated total VDR by 50-70% in rat intestine, LLC-PK1, and T-47D cells. The biological activity of 24-epi-1,25-D2 was found to be only 30-70% of 1,25-D3 and 1,25-D2 as determined by in vivo induction of intestinal calcium transport and bone calcium resorption in the rat and in vitro induction of 23- and 24-hydroxylase activities in T-47D cells. In vivo tracer kinetic studies demonstrated that in the rat 1,25-D3 and 1,25-D2 kinetics were similar, whereas 24-epi-1,25-D2 had a 25% shorter plasma half-life and was cleared from the body 2.8 times faster than the natural hormones. This more rapid clearance of 24-epi-1,25-D2 along with reduced VDR binding appears to explain the reduced biological activity of 24-epi-1,25-D2. Our data clearly demonstrate that although there are differences in side chain structure between 1,25-D2 and 1,25-D3, the VDR binding, biological activity, and whole body tracer kinetics of these two metabolites are virtually identical. However, movement of the 28 methyl of 1,25-D2 from its natural S configuration to the R configuration significantly alters the activity of this hormone.
Animals↗
Ketoconazole inhibits self-induced metabolism of 1,25-dihydroxyvitamin D3 and amplifies 1,25-dihydroxyvitamin D3 receptor up-regulation in rat osteosarcoma cells.
Ketoconazole (an inhibitor of vitamin D-24 hydroxylase) was used to study the role of self-induced 1,25-dihydroxyvitamin D3 (1,25-D3) metabolism on cellular responsiveness to 1,25-D3. Eighteen hours of treatment with 1,25-dihydroxy-[26,27-methyl-3H]vitamin D3 (1,25-[3H]D3) increased total 1,25-D3 receptors (VDR) from 60 to 170 fmol mg/protein. In cells treated with both 1,25-[3H]D3 and ketoconazole, up-regulation of VDR was increased by 40% over that observed with cells receiving 1,25-[3H]D3 alone. Ketoconazole alone had no agonistic activity. Treatment of cells with 1 nM 1,25-[3H]D3 plus increasing doses of ketoconazole (0-30 microM) resulted in a dose-dependent increase in occupied VDR and total VDR. This up-regulation was associated with reduced 1,25-[3H]D3 catabolism. 1,25-[3H]D3-induced up-regulation of VDR typically peaked at 14 h and declined thereafter. Ketoconazole lengthened the time to reach peak VDR up-regulation to 20 h. The ability of ketoconazole to increase cell responsiveness (VDR up-regulation) was the result of both increased and prolonged occupancy of VDR by 1,25-[3H]D3. The t1/2 of occupied VDR was 2 h in the absence of ketoconazole and greater than 7 h when ketoconazole was present. Collectively, these results suggested that self-induced catabolism of 1,25-D3 is an important regulator of VDR occupancy and therefore cellular responsiveness to hormone. These data also demonstrate the usefulness of ketoconazole as an inhibitor of vitamin D hydroxylases in intact cells.
Animals↗
Recurring hypocalcemia of bovine parturient paresis is associated with failure to produce 1,25-dihydroxyvitamin D.
Parturient paresis (milk fever) is a hypocalcemic disorder caused by the onset of lactation in the dairy cow. In most cows a complete recovery follows a single iv calcium treatment to correct the acute hypocalcemia. However, about 20% of cows treated for parturient paresis experience recurring episodes of hypocalcemia (relapses) requiring further treatment. Analysis of plasma from 8 nonrelapsing parturient paretic and 11 relapsing parturient paretic cows revealed differences in plasma 1,25-dihydroxyvitamin D [1,25-(OH)2D] concentrations before and during the development of hypocalcemia. In nonrelapsing cows, plasma 1,25-(OH)2D increased to 4- to 5-fold as plasma calcium concentrations declined during the first stage of parturient paresis. In relapsing cows, decreases in plasma calcium concentrations during the first stage of parturient paresis were accompanied by just a 2- to 2.5-fold increase in plasma 1,25-(OH)2D. Plasma 1,25-(OH)2D eventually increased 4- to 5-fold in the relapsing cows, but this response was delayed 24-48 h compared with the response in the nonrelapsing cows. Plasma PTH concentration profiles were similar in relapsing and nonrelapsing cows, suggesting that renal 25-hydroxyvitamin D 1 alpha-hydroxylase was temporarily refractory to stimulation by PTH in the relapsing cows. In both groups of cows recovery from parturient paresis began about 12-24 h after plasma 1,25-(OH)2D concentrations had increased 4- to 5-fold. These data imply that lack of production of 1,25-(OH)2D is an important factor in predisposing the cow to relapses of parturient paresis and is critical for recovery from the hypocalcemia associated with the onset of lactation.
Animals↗
Periparturient hypocalcemia in cows: prevention using intramuscular parathyroid hormone.
Intravenously administered parathyroid hormone has recently been reported to prevent parturient paretic hypocalcemia in dairy cows. In the present study, Parathyroid hormone was administered intramuscularly prior to parturition to study its effects on Ca homeostasis and the incidence of periparturient hypocalcemia. Ten Holstein cows were fed a high Ca diet prepartum to predispose them to parturient paretic hypocalcemia. Five cows received intramuscular injections of synthetic bovine parathyroid hormone three times per day beginning about 6 d before parturition and continuing at a reduced dose for about 6 d after parturition. One of five control cows developed parturient paresis, and all five control cows exhibited hypocalcemia within 24 h of calving. None of the treated cows became paretic, and plasma calcium was normal or slightly elevated in these cows during the first 24 h after calving. Parathyroid hormone administration increased plasma concentrations of 1,25-dihydroxyvitamin D and hydroxyproline prior to parturition, suggesting that both intestinal Ca absorption and bone calcium resorption were increased by administration of the hormone. One hormone-treated cow became recumbent and required euthanasia. Although metastatic calcification of soft tissues was not observed, the death of this cow raises the possibility that there are unknown side effects of parathyroid hormone when administered intramuscularly.
Animals↗
Parturient hypocalcemia in jersey cows fed alfalfa haylage-based diets with different cation to anion ratios.
Jersey cows were fed three alfalfa haylage-based diets with different cation-anion balances beginning 6 wk preceding third or later calving and ending 24 to 36 h postpartum. Sodium and Cl as percentages of dietary DM were .08 and 1.66 in diet 1 (anionic, 5 cows), .44 and .91 in diet 2 (intermediate, 6 cows), and 1.60 and .34 in diet 3 (cationic, 6 cows). Cation-anion balances were 22, 60, and 126 meq/100 g DM; Ca:P ratios averaged 4:1. Cows fed diet 1 in comparison with cows fed diets 2 or 3 over 6 wk had similar concentrations of Ca, P, and Na but higher concentrations of Mg and K in plasma and higher urinary excretions of Ca and Mg. Concentrations of 1,25-dihydroxyvitamin D 3 d before parturition were higher in cows fed diet 1 than in cows fed diets 2 or 3. Within 36 h after calving, mean concentrations of Ca in plasma (mg/dl, range) of cows fed diets 1 to 3, respectively, were 7 (8.7 to 6.2), 6.5 (7.8 to 3.9), and 6.3 (7.8 to 3.8). Number of cases of clinical milk fever by diet were 0 of 5, 2 of 6, and 1 of 6 cows. Alteration of dietary cation-anion balance by addition of Cl may effectively reduce incidence and severity of parturient hypocalcemia.
Animal Feed↗
Effects of continuous administration of 1,25-dihydroxyvitamin D3 on plasma minerals and unoccupied colon mucosal 1,25-dihydroxyvitamin D3 receptor concentrations.
Six mature nonlactating, nonpregnant Jersey cows were implanted with Alzet mini-osmotic pumps, which delivered 50 micrograms of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] each day for 7 d in an effort to mimic plasma concentrations of 1,25-dihydroxyvitamin D [1,25-(OH)2D] observed in cows at parturition. Plasma samples were obtained daily beginning 6 d prior to implantation and ending 8 d after removal of the implants. Six biopsies of the descending colon mucosa were obtained per rectum before and after implantation and assayed for unoccupied 1,25-(OH)2D3 receptor concentration. Plasma concentration of 1,25-(OH)2D increased from 37 pg/ml pretreatment to 294 pg/ml with the pumps implanted. Plasma Ca concentration increased within 2 d after implantation and remained elevated for 7 d after the pumps were removed. Unoccupied colon mucosa 1,25-(OH)2D3 receptor mean concentration prior to treatment was 14.6 fmol/mg protein and increased within 2 d following implantation to 30.5 fmol/mg protein. These data suggest that 1,25-(OH)2D3 upregulates its own receptor in the intestine of the cow.
Animals↗
24,26-Dihydroxyvitamin D2: a unique physiological metabolite of vitamin D2.
A new vitamin D2 metabolite, 24,26-dihydroxyvitamin D2, has been detected in the plasma of rats fed physiologic amounts of vitamin D2. The identity of the new metabolite (isolated from cow plasma) was established by ultraviolet absorbance, mass spectroscopy, chemical reactivity, and NMR spectroscopy. Among these, the mass spectrum was unique for the presence of a peak at M-48 that was attributed to an intramolecular rearrangement involving both the C-24 and C-26 hydroxyl groups. A 300-MHz 1H NMR spectrum of 40 micrograms of metabolite indicated a downfield shift of the C-28 methyl group signal to delta 1.30 and a multiplet at delta 3.66 corresponding to the hydroxylated C-26 methyl group. We determined that the formation of 24,26-dihydroxyvitamin D2 represented a major pathway for further metabolism of 24-hydroxyvitamin D2 in rats, exceeding the formation of 24,25-dihydroxyvitamin D2. Standard bioassays revealed that 24,26-dihydroxyvitamin D2 possessed very little biological activity and most likely represents a deactivation pathway for 24-hydroxyvitamin D2.
Animals↗
1,25-Dihydroxyvitamin D3 enhancement of concanavalin-A induced bovine lymphocyte proliferation: requirement of monocytes.
The effect of 1,25-(OH)2D3 on Concanavalin-A (ConA) mediated bovine lymphocyte proliferation was dependent on the magnitude of the proliferative response. Lymphocytes from cows with high inherent proliferative responses (134,904 +/- 15,488 cpm/well) were unaffected by 1,25-(OH)2D3; whereas, lymphocytes from cows with low inherent proliferative responses (46,317 +/- 6000 cpm/well) were stimulated 75% (P less than 0.01) by 10(-10)M 1,25-(OH)2D3. At low initial proliferation rates, seen with low density cultures enriched for lymphocytes, the effect of 1,25-(OH)2D3 on proliferation changed from inhibition in the absence of added monocytes to stimulation at 18-23% monocyte addition. These results suggest that 1,25-(OH)2D3 possesses both stimulatory and inhibitory effects on ConA-induced proliferation that are monocyte dependent.
Adjuvants, Immunologic↗
Effects of infusion of human parathyroid hormone-related protein-(1-40) in nude mice: histomorphometric and biochemical investigations.
Female nude mice were infused with 5.0, 3.0, or 1.0 micrograms/day of synthetic human parathyroid hormone-related protein (PTHrP) or control diluent with subcutaneous Alzet miniosmotic pumps for 7 days. Serum calcium was increased (p less than 0.01) on days 3 (13.9 mg/dl), 5 (13.6 mg/dl), and 7 (12.9 mg/dl) in mice infused with PTHrP at 5.0 micrograms/day compared with control nude mice (8.8 mg/dl). Serum calcium was significantly increased to a lesser degree in mice infused with 1.0 micrograms/day PTHrP (day 3) or 3.0 micrograms/day (days 3 and 7). Serum phosphorus was decreased (p less than 0.01) in all three groups of mice infused with PTHrP (4.6 mg/dl, 5.0 micrograms/day; 6.7 mg/dl, 3.0 micrograms/day; and 6.4 mg/dl, 1.0 micrograms/day) compared with controls (8.5 mg/dl). Serum 1,25-dihydroxycholecalciferol was increased (2.4-fold) in mice infused with PTHrP (5.0 and 3.0 micrograms/day). The urinary calcium-creatinine ratio (0.74 compared with 0.034 in controls) was increased (p less than 0.03) in mice infused with PTHrP (5.0 micrograms/day), but the urinary phosphorus-creatinine ratio was not different from that in controls. The urinary cAMP-creatinine ratio was increased (1.6-fold) in mice infused with PTHrP (5.0 micrograms/day). Static bone histomorphometry revealed increased (p less than 0.01) trabecular bone area, osteoblast perimeter, osteoid perimeter, osteoid width, wall width, osteoclast area, number of osteoclasts, and osteoclast perimeter in trabecular bone of lumbar vertebrae from mice infused with PTHrP. Dynamic bone histomorphometry demonstrated increased (p less than 0.01) double-labeled perimeter, mineralizing perimeter, and bone formation rate. The results of this study indicated that PTHrP increased serum calcium and 1,25-dihydroxycholecalciferol, decreased serum phosphorus, increased urinary excretion of calcium, phosphorus, and cAMP, and increased both bone resorption and formation in nude mice. PTHrP mimics the action of native PTH in vivo and is likely to be an important protein in the pathogenesis of humoral hypercalcemia of malignancy.
Animals↗
The biological assessment of vitamin D3 metabolites produced by rumen bacteria.
Biological assays were performed to evaluate 10-oxo-19-nor-vitamin D3 (10-oxo-D3) and 5(E) 25-hydroxy-10-oxo-19-nor-vitamin D3 (25-OH-10-oxo-D3) two bacterial products of vitamin D3 (D3) and 25-hydroxyvitamin D3 (25-OHD3) metabolism, respectively. The 5(Z) and 5(E) isomers of 10-oxo-D3 were, respectively, 40- and 80-fold less active than D3 in stimulating Ca+2 absorption from the gut. 25-Hydroxy-10-oxo-D3 did not stimulate Ca+2 absorption. Only 5(Z) 10-oxo-D3 induced mobilization of bone Ca+2. In addition, both 10-oxo-D3 and 25-OH-10-oxo-D3 showed poor affinities for either the plasma D3-binding protein or the thymus 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] receptor. 10-Keto-D3 exhibited a plasma half-life of only 6 min. This was a much shorter half-life than that exhibited by other vitamin D metabolites and was expected because of the poor affinity 10-oxo-D3 has for the plasma vitamin D binding protein. Bacterial metabolism of D3 deactivates the vitamin, which allows ruminants to tolerate relatively large oral doses of D3.
Animals↗
The effect of uninephrectomy on mineral metabolism in normal human kidney donors.
A longitudinal prospective study of 17 normal human kidney donors before and after uninephrectomy revealed changes in mineral metabolism during compensation for loss of renal mass. Increases in carboxy terminal parathyroid hormone (PTH) and urinary cyclic adenosine monophosphate (AMP) occurred at 1 week and persisted for up to 3 years after surgery. 1,25(OH)2D levels fell from 26.5 +/- 2.0 to 18.6 +/- 1.7 pg/mL (P less than 0.05) at 1 week. Tubular reabsorption of phosphate (TRP) fell from 83.4% to 72.3% at 1 month and remained at this level throughout the study. At 6 months, several changes developed that were suggestive of increased PTH effect: hypocalciuria, a decrease in serum phosphate, and the return of 1,25(OH)2D levels to baseline or above. 1,25(OH)2D levels showed an inverse correlation with serum phosphate at 6 months (r = 0.75, P less than 0.005) and 1 year (r = 0.60, P less than 0.01). In addition, at 6 months, an increase in bone mineral content by forearm photon absorptiometry was indirect evidence for a period of positive calcium balance. The compensatory changes demonstrated in this study after loss of renal mass took place over the course of several months and persisted for up to 3 years.
Adult↗
Calcium, phosphorus, and magnesium homeostasis in ruminants.
Significant advances have been made in the last 30 years in the understanding of Ca, PO4, and Mg homeostasis in ruminants. Despite these advances, the primary cellular or molecular lesions responsible for failure of homeostasis have yet to be identified. Suggested causes, such as primary hormone deficiencies, have been eliminated, and we now believe that aging and nutrition can reduce the ability of intestine, bone, and kidney to respond rapidly to the hormone signals responsible for homeostasis during rapid increases in demand for these minerals. Further research is required before these lesions can be identified and new knowledge applied to the development of economical, effective programs that prevent milk fever and hypomagnesemic tetany. Until then, diseases such as milk fever will continue to affect 8 to 9 per cent of our dairy cows, and dairy farmers will continue to spend millions of dollars a year for treatment of the primary disease and the many secondary problems that result from these diseases.
Animals↗
Metabolic bone disease of total parenteral nutrition: course after changing from casein to amino acids in parenteral solutions with reduced aluminum content.
Bone disease with total parenteral nutrition (TPN) has been attributed to aluminum loading or vitamin D therapy. We studied 17 patients who first received TPN containing casein hydrolysate with high Al and ergocalciferol (25 micrograms/d) for 6-72 mo followed by TPN containing amino acids with reduced Al and ergocalciferol (5 micrograms/d) for 9-58 mo. We also did a cross-sectional study of 22 patients receiving casein and ergocalciferol (25 micrograms/d) compared with 46 patients receiving amino acids and ergocalciferol (5 micrograms/d) for 6-58 mo. Bone formation was higher and osteoid area, bone-surface stainable Al and total bone Al were lower with amino acid TPN than with casein TPN. Bone formation varied inversely with both plasma Al and bone-surface Al, suggesting that plasma or bone-surface Al, acquired during TPN, can reduce bone formation and lead to patchy osteomalacia. Serum levels of iPTH and 1,25-dihydroxyvitamin D were higher with amino acid TPN.
Aluminum↗
Evidence that discrimination against ergocalciferol by the chick is the result of enhanced metabolic clearance rates for its mono- and dihydroxylated metabolites.
Studies on the discrimination between ergocalciferol (vitamin D2) and cholecalciferol (vitamin D3) by chickens have led to conflicting conclusions. To investigate this problem in more detail, radiolabeled vitamin D and vitamin D metabolites were administered intravenously, which allowed determination of their relative plasma clearance rates. The study involved three groups of adult male chickens (five per group). Birds in group 1 were co-dosed with [3H]vitamin D2 and [3H]vitamin D3. Birds in group 2 were co-dosed with [3H]25-dihydroxyvitamin D2 and [3H]25-dihydroxyvitamin D3 and birds in group 3 were co-dosed with [3H]1,25-dihydroxyvitamin D3 and [3H]1,25-dihydroxyvitamin D2. The results indicated that the plasma turnover rate of [3H]vitamin D2 is 1.5 times faster than that of [3H]vitamin D3. Plasma turnover of the 25-hydroxylated metabolites differed, with [3H]25-dihydroxyvitamin D2 clearing faster (11 times) than [3H]25-dihydroxyvitamin D3. The largest difference appeared in the 1,25-dihydroxyvitamin D2 turnover rates with 1,25-dihydroxyvitamin D2 clearing approximately 33 times faster then [3H]1,25-dihydroxyvitamin D3. These data, therefore, indicate that discrimination against vitamin D2 sterols in the chick occurs primarily between steps in the metabolism of vitamin D and not at the point of metabolism or excretion of the parent vitamin.
25-Hydroxyvitamin D 2↗
Calcium transport and vitamin D in three breeds of spontaneously hypertensive rats.
Conflicting results have been published by different laboratories comparing the rate of intestinal calcium transport and concentration of circulating 1,25-dihydroxyvitamin D (1,25-[OH]2D) in the spontaneously hypertensive rat (SHR) and control Wistar-Kyoto rat (WKY): They have been reported to be greater, the same, or lower in the SHR than in the WKY. We tested the possibility that the conflicting results might be breeder-related by measuring 1) the rate of intestinal mucosal calcium transport, 2) the concentration of circulating 25-hydroxyvitamin D (25-OH-D) and 1,25-(OH)2D, and 3) the concentration of intestinal mucosal receptor for 1,25-(OH)2D in the two strains of animals from three different breeders. Sodium and water transport were also measured because of their relevance to hypertension. Blood pressure was always higher and calcium, as well as mean sodium and water transport, was always lower in the SHR than in the WKY. The concentration of 1,25-(OH)2D was the same, higher, or lower in the SHR than in the WKY and was age- and breeder-dependent. Mean mucosal 1,25-(OH)2D receptor concentration was higher in the SHR and was variable, depending on breeder. We conclude that 1) the rate of calcium transport is lower in the SHR than in the WKY and independent of breeder and concentration of 1,25-(OH)2D in serum, 2) the variability in 1,25-(OH)2D concentration among investigators may be breeder-dependent, and 3) the higher receptor concentration in the intestinal mucosa of the SHR could be a compensatory response to the decreased rate of calcium transport. These differences in calcium and sodium transport may be an expression in the enterocyte of factors etiological for hypertension.
Animal Husbandry↗
Use of 24-F-1,25-dihydroxyvitamin D3 to prevent parturient paresis in dairy cows.
Forty-one aged Jersey cows were fed a high Ca diet prior to parturition to predispose them to parturient paresis. Twenty-one of the cows were treated with 24-F-1,25-dihydroxyvitamin D3, a synthetic analogue of 1,25-dihydroxyvitamin D3, 7 d before the expected parturition. Treated cows received either 100 micrograms (n = 7) or 150 micrograms (n = 14) of 24-F-1,25-dihydroxyvitamin D3, intramuscularly at 7-d intervals until the cow calved. Incidence of parturient paresis among untreated animals was 85% (17/20). Injections of 100 micrograms of 24-F-1,25-dihydroxyvitamin D3 reduced the incidence of parturient paresis to 43% (3/7), whereas 150 micrograms injections of 24-F-1,25-dihydroxyvitamin D3 reduced the incidence of parturient paresis to 29% (4/14). Plasma concentrations of hydroxyproline were not elevated prior to parturition in 24-F-1,25-dihydroxyvitamin D3-treated cows, indicating that treatment did not stimulate bone resorption and that the ability of 24-F-1,25-dihydroxyvitamin D3 to prevent parturient paresis likely resides in its ability to stimulate intestinal Ca absorption prior to parturition. Further, cows treated with 24-F-1,25-dihydroxyvitamin D3 that developed parturient paresis had lower than normal plasma concentrations of 1,25-dihydroxyvitamin D, indicating that 24-F-1,25-dihydroxyvitamin D3 treatment impairs the metabolism of 25-hydroxyvitamin D in response to hypocalcemia. These data suggest that injection of 24-F-1,25-dihydroxyvitamin D3, delivered at 7-d intervals prior to parturition, can effectively reduce incidence of parturient paresis in dairy cows.
Animals↗