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

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.

1988 ◽  
Vol 250 (3) ◽  
pp. 671-677 ◽  
Author(s):  
T Matsumoto ◽  
K Ikeda ◽  
H Yamato ◽  
K Morita ◽  
I Ezawa ◽  
...  

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.


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.


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.


1984 ◽  
Vol 246 (2) ◽  
pp. E168-E173 ◽  
Author(s):  
Y. Tanaka ◽  
H. F. DeLuca

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.


1982 ◽  
Vol 243 (6) ◽  
pp. F570-F575 ◽  
Author(s):  
D. A. Bushinsky ◽  
M. J. Favus ◽  
A. B. Schneider ◽  
P. K. Sen ◽  
L. M. Sherwood ◽  
...  

To study the effects of chronic metabolic acidosis on the metabolism of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] rats were given either a low calcium diet (LCD) (0.002% calcium) or chow (1.2% calcium); ammonium chloride (NH4Cl) was added (1 or 1.5%) to the drinking water of some rats eating LCD or chow while others served as nonacidotic controls. LCD increased circulating 1,25(OH)2D3 levels from 46 +/- 14 to 204 +/- 24 pg/ml (P less than 0.001) in the absence of NH4Cl; 1.5% NH4Cl prevented the increase in 1,25(OH)2D3 (25 +/- 6 vs. 27 +/- 8 pg/ml (P, NS) but 1% NH4Cl did not (50 +/- 12 vs. 161 +/- 23 pg/ml; P less than 0.001). Acidosis suppressed neither serum immunoreactive parathyroid hormone (PTH) nor urine cAMP response to LCD. Although total serum calcium and phosphorus showed no regular changes with NH4Cl, acidosis raised blood ionized calcium in rats fed either chow or LCD, and serum 1,25(OH)2D3 levels were inversely correlated with ionized calcium (r = 0.714; P less than 0.001) during LCD. Chronic NH4Cl acidosis prevented serum 1,25(OH)2D3 from rising during LCD, independent of changes in PTH secretion, cAMP generation, or serum phosphorus. The absence of a 1,25(OH)2D3 response may be due to increased ionized calcium produced by acidosis.


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