scholarly journals Chronic 1,25-dihydroxyvitamin D3 administration in the rat reduces the serum concentration of 25-hydroxyvitamin D by increasing metabolic clearance rate.

1986 ◽  
Vol 78 (3) ◽  
pp. 622-628 ◽  
Author(s):  
B P Halloran ◽  
D D Bikle ◽  
M J Levens ◽  
M E Castro ◽  
R K Globus ◽  
...  
1987 ◽  
Vol 253 (3) ◽  
pp. E246-E250
Author(s):  
R. Eastell ◽  
B. L. Riggs ◽  
R. Kumar

We have developed a rapid primed-infusion technique for the measurement of the metabolic clearance and production rate of 1,25-dihydroxyvitamin D3 in normal human subjects and experimental animals. With this method, an estimate of the metabolic clearance rate of 1,25-dihydroxyvitamin D3 can generally be made within 3 to 4 h. Initial studies in five dogs using 1,25-[3H]-dihydroxyvitamin D3 (180 Ci/mmol) allowed us to determine the optimal ratio of loading dose to infusion rate that resulted in the most rapid attainment of steady-state levels of plasma radioactivity. By use of this technique we found that the metabolic clearance rate of 1,25-dihydroxyvitamin D3 in dogs was 6.3 +/- 1.2 ml/min (mean +/- SD); the production rate of the hormone was 0.40 +/- 0.25 microgram/day (20.4 +/- 14.4 ng . kg-1 . day-1). In eight normal women, aged 28-51 yr, the metabolic clearance rate for 1,25-dihydroxyvitamin D3 was 25.9 +/- 4.7 ml/min; the production rate was 1.38 +/- 0.45 microgram/day (20.7 ng . kg-1 . day-1). The advantages of this method relative to ones used in the past are that it can be performed quickly (generally within 3-4 h) with the use of only tracer amounts of this hormone (equivalent to 1.1% of the production rate). With this method, no assumptions about the most appropriate model to which to fit the data need to be made. Because of its rapidity, no metabolites of the injected 1,25-dihydroxyvitamin D3 are formed during the study interval.


1989 ◽  
Vol 256 (5) ◽  
pp. E686-E691
Author(s):  
B. P. Halloran ◽  
M. E. Castro

Administration of 1,25-dihydroxyvitamin D [1,25(OH)2D] can increase the metabolic clearance rate (MCR) of 25-hydroxyvitamin D [25(OH)D]. To determine whether administration of 1,25(OH)2D can also influence the metabolic clearance rates (MCR) of 1,25(OH)2D and 24,25-dihydroxyvitamin D 24,25(OH)2D, we measured metabolic clearance of 1,25(OH)2D, 24,25(OH)2D, and 25(OH)D in rats in which the serum concentration of 1,25(OH)2D was increased by continuous infusion. Infusion of 1,25(OH)2D (12 days at 75 pmol/day) increased serum 1,25(OH)2D from 128 +/- 11 to 244 +/- 14 pg/ml (P less than 0.005) and increased MCR from 169 +/- 13 to 210 +/- 9 microliters.min-1.kg-1 or 24% (P less than 0.025). Increasing serum 1,25(OH)2D to 330-360 pg/ml increased MCR 72%. Infusion of 1,25(OH)2D decreased serum 24,25(OH)2D from 3.5 +/- 0.5 to 2.4 +/- 0.3 ng/ml (P less than 0.05), increased MCR from 25 +/- 2 to 48 +/- 6 microliters.min-1.kg-1 (P less than 0.0025), and increased the production rate (PR) from 70 +/- 11 to 124 +/- 26 pg.min-1.kg-1 (P less than 0.05). Infusion of 1,25(OH)2D decreased serum 25(OH)D from 13.0 +/- 0.5 to 8.0 +/- 0.5 ng/ml (P less than 0.005) and increased MCR from 45 +/- 1 to 75 +/- 7 microliters.min-1.kg-1 (P less than 0.001) but had no effect on PR. The data indicate that increasing serum 1,25(OH)2D by chronic administration can increase the MCR of 1,25(OH)2D and suggest that 1,25(OH)2D can feedback regulate its serum concentration by regulating its MCR. The data also suggest that 1,25(OH)2D administration can increase the MCRs of 24,25(OH)2D and 25(OH)D.


1985 ◽  
Vol 69 (5) ◽  
pp. 549-552
Author(s):  
John Fox ◽  
Anthony D. Care

1. We have used pigs with inherited vitamin D-dependent rickets type 1 to study the effect of 1,25-dihydroxyvitamin D deficiency on the metabolic clearance rate of 3H-1,25-dihydroxyvitamin D3 infused to steady-state levels in plasma. 2. Plasma levels of 1,25-dihydroxyvitamin D were 24 ± 1 (sem) pmol/l in the hypocalcaemic, homozygous piglets and 196 ± 27 pmol/l in their normocalcaemic, heterozygous siblings. 3. The metabolic clearance rate of 1,25-dihydroxyvitamin D3 was the same in both normal heterozygous (0.90 ± 0.02) and hypocalcaemic, homozygous piglets (0.90±0.01 ml−1 min−1 kg−1 metabolic bodysize). 4. We conclude that a deficiency of circulating 1,25-dihydroxyvitamin D does not influence the clearance of 1,25-dihydroxyvitamin D3 from the circulation of pigs.


1984 ◽  
Vol 107 (1) ◽  
pp. 141-144 ◽  
Author(s):  
B. Eiben ◽  
St. Scharla ◽  
K. Fischer ◽  
H. Schmidt-Gayk

Abstract. Serum 1,25-dihydroxyvitamin D3 and serum alkaline phosphatase increased several fold during the antler formation period in July. Both maxima were observed in the second half of the antler formation period, where the mineralization of the antler takes place. In contrast serum levels of calcium and 25-hydroxyvitamin D3 showed no alternation or seasonal variation.


1990 ◽  
Vol 259 (5) ◽  
pp. E665-E671 ◽  
Author(s):  
B. Lobaugh ◽  
A. Boass ◽  
G. E. Lester ◽  
S. U. Toverud

To characterize further the mechanism(s) underlying the increased serum 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] concentration associated with lactation in the rat, we examined hormone biosynthesis [i.e., renal 25-hydroxyvitamin D-1 alpha-hydroxylase (1 alpha-hydroxylase) activity] and hormone disappearance in groups of lactating Holtzman rats and age- and sex-matched nonlactating controls. 1 alpha-Hydroxylase activity was significantly greater in kidneys from lactating rats (4.0 +/- 0.42 fmol.mg-1.min-1) on a basal diet than in those from nonmated females (1.4 +/- 0.08 fmol.mg-1.min-1), an increment sufficient to account for the observed fourfold elevation of 1,25(OH)2D3 in the dams. The increase occurs despite the lower serum 1,25(OH)2D3 levels in lactating than in nonlactating rats at 12 and 24 h after a bolus injection of 1,25(OH)2D3 (2 ng/g body wt). Elevation of serum 1,25(OH)2D3 is not a requisite consequence of lactation, however, because dams receiving supplemental calcium from food (1.6%) and water (0.3%) exhibited no increase of either serum 1,25(OH)2D3 or 1 alpha-hydroxylase activity compared with controls. In contrast, lactating rats that received a diet with only 0.1% calcium had 5-fold higher serum 1,25(OH)2D3 levels and 20-fold higher 1 alpha-hydroxylase activity than nonlactating rats on the same diet. We conclude that other factors in conjunction with lactation, but not the lactating state per se, promote the changes in 1,25(OH)2D3 metabolism observed.


1982 ◽  
Vol 243 (5) ◽  
pp. E370-E374 ◽  
Author(s):  
R. Kumar ◽  
R. Wiesner ◽  
M. Scott ◽  
V. L. Go

We determined the metabolic clearance and production rates of 24,25-dihydroxyvitamin D3 in four normal healthy adults. We also examined the excretion of radioactivity in stool, urine, and bile after the intravenous administration of 24,25-[3H]dihydroxyvitamin D3 to human subjects. 24,25-Dihydroxyvitamin D3 is rapidly cleared from the plasma with a half-life of approximately 390 +/- 25 min (mean +/- SE). The metabolic clearance rate of 24,25-dihydroxyvitamin D3 was 9.2 +/- 1.5 liters/day with a production rate of 26.4 +/- 7.2 micrograms/day (mean +/- SE). Within 1 day 13.0 +/- 4.2% (mean +/- SE) of the administered dose had appeared in the stool; by day 7, 48.8 +/- 2.7% of the dose had appeared in the feces. Within 24 hr, 6.4 +/- 0.8% of the administered dose appeared in the urine; 7.4 +/- 1.8% of the dose had appeared in the urine within 2 days. The biliary excretion of 24,25-dihydroxyvitamin D3 was studied in two subjects. By 8 h, 15.3 +/- 1.3% of the administered dose had appeared in the bile. The metabolites present in bile, feces, and urine were much more polar than 24,25-dihydroxyvitamin D3. These results demonstrate that 24,25-dihydroxyvitamin D3 is rapidly cleared from plasma and is excreted in the feces (probably via the bile) and urine of normal human subjects.


1983 ◽  
Vol 214 (3) ◽  
pp. 893-897 ◽  
Author(s):  
Y Tanaka ◽  
H F DeLuca

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.


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