Effect of low phosphorus and low calcium diets on the production and metabolic clearance rates of calcitriol (1,25-dihydroxyvitamin D3) in vivo in pigs

Bone ◽  
1985 ◽  
Vol 6 (1) ◽  
pp. 54-55
Author(s):  
J. Fox ◽  
R. Ross ◽  
A.D. Care
Keyword(s):  
Metabolic Clearance ◽  
Clearance Rates ◽  
Dihydroxyvitamin D3 ◽  
1,25 Dihydroxyvitamin D3 ◽  
Low Calcium ◽  
Low Phosphorus

Rat renal 25-hydroxyvitamin D3 1- and 24-hydroxylases: their in vivo regulation

1984 ◽  
Vol 246 (2) ◽  
pp. E168-E173 ◽  
Author(s):  
Y. Tanaka ◽  
H. F. DeLuca
Keyword(s):  
Vitamin D ◽  
Inorganic Phosphorus ◽  
Hydroxylase Activity ◽  
Deficient Diet ◽  
Dihydroxyvitamin D3 ◽  
1,25 Dihydroxyvitamin D3 ◽  
Dietary Phosphorus ◽  
Low Calcium

The effects of thyroparathyroidectomy, parathyroid hormone, 1,25-dihydroxyvitamin D3, dietary calcium, dietary phosphorus, age, and sex on the renal 25-hydroxyvitamin D3 1- and 24-hydroxylases measured in vitro in rats have been studied. Thyroparathyroidectomy of vitamin D-deficient rats abolishes 25-hydroxyvitamin D3 1-hydroxylase activity, and administration of bovine parathyroid extract to the thyroparathyroidectomized rat restores diminished 1-hydroxylase activity. Both suppression and restoration of the enzyme activities require many hours (18-24 h) independent of rapid changes in serum calcium and inorganic phosphorus levels in response to these manipulations. Administration of 1,25-dihydroxyvitamin D3 to vitamin D-deficient rats suppresses 25-hydroxyvitamin D3 1-hydroxylase activity and stimulates 25-hydroxyvitamin D3 24-hydroxylase activity within 48 h. Rats maintained on a low-calcium or a low-phosphorus diet with a daily supplement of 20 IU vitamin D3 show high 25-hydroxyvitamin D3 1-hydroxylase activity and low 24-hydroxylase activity as compared with rats similarly treated but fed a diet containing adequate calcium or adequate phosphorus. When vitamin D-sufficient rats having suppressed renal 25-hydroxyvitamin D3 1-hydroxylase activity are placed on a low-calcium vitamin D-deficient diet for 7 days, the 1-hydroxylase activity is greatly stimulated in 6-wk-old rats but much less so in rats with advancing age.

scholarly journals Stimulation of 1,25-dihydroxyvitamin D3 production by 1,25-dihydroxyvitamin D3 in the hypocalcaemic rat

1983 ◽  
Vol 214 (3) ◽  
pp. 893-897 ◽  
Author(s):  
Y Tanaka ◽  
H F DeLuca
Keyword(s):  
Vitamin D3 ◽  
Hydroxylase Activity ◽  
Dihydroxyvitamin D3 ◽  
Hydroxyvitamin D ◽  
1,25 Dihydroxyvitamin D3 ◽  
Calcium Diet ◽  
Low Calcium Diet ◽  
Low Calcium ◽  
Low Phosphorus ◽  
25 Hydroxyvitamin D

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.

scholarly journals 1,25-Dihydroxyvitamin D3 up-regulates the 1,25-dihydroxyvitamin D3 receptor in vivo.

1989 ◽  
Vol 86 (24) ◽  
pp. 9770-9773 ◽  
Author(s):  
M. Strom ◽  
M. E. Sandgren ◽  
T. A. Brown ◽  
H. F. DeLuca
Keyword(s):  
D3 Receptor ◽  
Dihydroxyvitamin D3 ◽  
1,25 Dihydroxyvitamin D3

Characterization of 1,25-dihydroxyvitamin D3 receptors and in vivo targeting of [3H]-1,25(OH)2D3 in the sheep placenta

Placenta ◽  
1989 ◽  
Vol 10 (6) ◽  
pp. 553-567 ◽  
Author(s):  
Richardus Ross ◽  
Jane Florer ◽  
Kevin Halbert ◽  
Lori McIntyre
Keyword(s):  
Dihydroxyvitamin D3 ◽  
D3 Receptors ◽  
1,25 Dihydroxyvitamin D3

Biological activity of 24,24-difluoro-1,25-dihydroxyvitamin D3

1983 ◽  
Vol 244 (2) ◽  
pp. E159-E163
Author(s):  
S. Okamoto ◽  
Y. Tanaka ◽  
H. F. DeLuca ◽  
Y. Kobayashi ◽  
N. Ikekawa
Keyword(s):  
Biological Activity ◽  
Calcium Transport ◽  
Plasma Calcium ◽  
Epiphyseal Plate ◽  
Dihydroxyvitamin D3 ◽  
Responsive Systems ◽  
1,25 Dihydroxyvitamin D3 ◽  
Bone Calcium ◽  
Calcium And Phosphorus

The biological activity of 24,24-difluoro-1,25-dihydroxyvitamin D3 was compared with 1,25-dihydroxyvitamin D3 in the rat. The 24,24-difluoro-1,25-dihydroxyvitamin D3 has a potency of approximately 5-10 times that of 1,25-dihydroxyvitamin D3 in the known in vivo vitamin D responsive systems. These systems include intestinal calcium transport, bone calcium mobilization, calcification of epiphyseal plate cartilage, and elevation of plasma calcium and phosphorus concentrations. Thus, 24,24-difluoro-1,25-dihydroxyvitamin D3 is the first known analogue with higher potency than 1,25-dihydroxyvitamin D3 in vivo.

A primed-infusion technique for rapid estimation of the metabolic clearance rate of 1,25(OH)2D3

1987 ◽  
Vol 253 (3) ◽  
pp. E246-E250
Author(s):  
R. Eastell ◽  
B. L. Riggs ◽  
R. Kumar
Keyword(s):  
Production Rate ◽  
Clearance Rate ◽  
Human Subjects ◽  
Metabolic Clearance ◽  
Metabolic Clearance Rate ◽  
Dihydroxyvitamin D3 ◽  
1,25 Dihydroxyvitamin D3 ◽  
Study Interval ◽  
Normal Women ◽  
Infusion Technique

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.

scholarly journals Effect of 24,25-dihydroxyvitamin D3 on 1,25-dihydroxyvitamin D3 metabolism in calcium-deficient rats

1988 ◽  
Vol 250 (3) ◽  
pp. 671-677 ◽  
Author(s):  
T Matsumoto ◽  
K Ikeda ◽  
H Yamato ◽  
K Morita ◽  
I Ezawa ◽  
...  
Keyword(s):  
Cyclic Amp ◽  
Water Soluble ◽  
Considerable Proportion ◽  
Dihydroxyvitamin D3 ◽  
1,25 Dihydroxyvitamin D3 ◽  
Calcium Diet ◽  
Low Calcium Diet ◽  
Low Calcium ◽  
Urinary Cyclic Amp ◽  
24,25 Dihydroxyvitamin D3

The effect of 24,25-dihydroxyvitamin D3 [24,25(OH)2D3] on 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] metabolism was examined in rats fed on a low-calcium diet. These rats exhibit hypocalcaemia, high urinary cyclic AMP excretion, a markedly elevated serum 1,25(OH)2D concentration and low serum concentrations of both 24,25(OH)2D and 25(OH)D. When the rats are treated orally with 1, 5 or 10 micrograms of 24,25(OH)2D3/100 g every day, there is a dramatic decrease in serum 1,25(OH)2D concentration in a dose-dependent manner concomitant with an increase in serum 24,25(OH)2D concentration. Serum calcium concentration and urinary cyclic AMP excretion are not significantly affected by the 24,25(OH)2D3 treatment, which suggests that parathyroid function is not affected by the 24,25(OH)2D3 treatment. The 25(OH)D3 1 alpha-hydroxylase activity measured in kidney homogenates is markedly elevated in rats on a low-calcium diet but is not affected by any doses of 24,25(OH)2D3. In contrast, recovery of intravenously injected [3H]1,25(OH)2D3 in the serum is decreased in 24,25(OH)2D3-treated rats. Furthermore, when [3H]1,25(OH)2D3 is incubated in vitro with kidney or intestinal homogenates of 24,25(OH)2D3-treated rats there is a decrease in the recovery of radioactivity in the total lipid extract as well as in the 1,25(OH)2D3 fraction along with an increase in the recovery of radioactivity in the water-soluble phase. These results are consistent with the possibility that 24,25(OH)2D3 has an effect on 1,25(OH)2D3 metabolism, namely that of enhancing the degradation of 1,25(OH)2D3. However, because a considerable proportion of the injected 24,25(OH)2D3 is expected to be converted into 1,24,25(OH)3D3 by renal 1 alpha-hydroxylase in 24,25(OH)2D3-treated rats, at least a part of the decrease in serum 1,25(OH)2D concentration may be due to a competitive inhibition by 24,25(OH)2D3 of the synthesis of 1,25(OH)2D3 from 25(OH)D3. Thus the physiological importance of the role of 24,25(OH)2D3 in regulating the serum 1,25(OH)2D concentration as well as the mechanism and metabolic pathway of degradation of 1,25(OH)2D3 remain to be clarified.

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