Impaired metabolism of 1,25(OH)2D3 in chicks treated with EHDP and subsisted on 1,25(OH)2D3 as their sole source of vitamin D

Decreased intestinal absorption of Ca2+ occurs in response to treatment with disodium ethane-1-hydroxy-1,1-diphosphonate (EHDP). The effect is due to decreased 1-hydroxylation of calcidiol (25-hydroxycholecalciferol) in the kidney. In an attempt to establish whether impairment of vitamin D metabolism at steps beyond kidney hydroxylation occurs due to treatment with EHDP, chicks were depleted of vitamin D and were treated with calcitriol (1,25-dihydroxycholecalciferol) as their sole source of the vitamin. The chicks were then divided into two groups, one being treated with EHDP while the second group served as control. Intestinal absorption of Ca2+ in the EHDP-treated group was found to be impaired, along with decreases in concentrations of calbindin D28K (the 28,000-Mr vitamin D-dependent Ca2+-binding protein). When the chicks were dosed with [3H]calcitriol, significantly lower concentrations of the sterol were detected in the duodena of EHDP-treated birds. Measurement of levels of receptors for calcitriol in duodena showed no difference between groups, but levels of calcitriol in sera were considerably lower in the EHDP-treated group along with the elevated biliary and urinary excretion of glucuronidated conjugates. It is therefore concluded that treatment with EHDP results in increased catabolism of calcitriol in addition to the known suppression of the renal production of the hormone.

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1- but not 24-hydroxylation of vitamin D is required for skeletal mineralization in rats

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1983.244.3.e298 ◽

1983 ◽

Vol 244 (3) ◽

pp. E298-E304

Author(s):

R. Brommage ◽

K. Jarnagin ◽

H. F. DeLuca ◽

S. Yamada ◽

H. Takayama

Keyword(s):

Vitamin D ◽

Sole Source ◽

Female Rats ◽

Male Rats ◽

Constant Infusion ◽

Dihydroxyvitamin D3 ◽

1,25 Dihydroxyvitamin D3 ◽

Male And Female Rats ◽

Normal Body Weight ◽

Skeletal Mineralization

To evaluate the importance of 1- and 24-hydroxylation of 25-hydroxyvitamin D3 on skeletal mineralization, male and female rats from vitamin D-deficient mothers were administered from weaning either 100 pmol/day of 25-hydroxyvitamin D3, 50 pmol/day of 1,25-dihydroxyvitamin D3, or 100 pmol/day of 24,24-difluoro-25-hydroxyvitamin D3 as their sole source of vitamin D. A separate group of rats did not receive any vitamin D. 1,25-Dihydroxyvitamin D3 was given by constant infusion at a dose that normalized plasma calcium concentrations and produced normal body weight gains. Skeletal mineralization was studied by determining femur organic and ash weights. Femurs were obtained from male rats 6 wk after weaning, from female rats at conception, at the end of lactation, and 6 wk after lactation, and from weanling pups born to the female rats. No striking differences in femur organic and ash weights were found between 25-hydroxyvitamin D3 groups and either the 1,25-dihydroxyvitamin D3 group or the 24,24-difluoro-25-hydroxyvitamin D3 group, whereas the vitamin D-deficient rats had poorly mineralized femurs. These results indicate that 1,25-dihydroxyvitamin D3 at a lower dose is as fully active as 25-hydroxyvitamin D3 in promoting skeletal mineralization in the rat and that preventing the 24-hydroxylation of 25-hydroxyvitamin D3 by administering 24,24-difluoro-25-hydroxyvitamin D3 does not elicit any obvious skeletal abnormality, especially on mineralization.

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Effect of vitamin D3 metabolites on calcium and phosphorus metabolism in chick embryos

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1985.248.3.e281 ◽

1985 ◽

Vol 248 (3) ◽

pp. E281-E285 ◽

Cited By ~ 2

Author(s):

L. E. Hart ◽

H. F. DeLuca

Keyword(s):

Vitamin D ◽

Embryonic Development ◽

Vitamin D3 ◽

Chorioallantoic Membrane ◽

Sole Source ◽

Chick Embryos ◽

Dihydroxyvitamin D3 ◽

Total Body Calcium ◽

1,25 Dihydroxyvitamin D3 ◽

24,25 Dihydroxyvitamin D3

The biochemical nature of the physiological defect found in chick embryos from hens supported on 1,25-dihydroxyvitamin D3 as their sole source of vitamin D is described. Vitamin D-deficient hens (44-wk-old) were divided into six groups of five and dosed daily for 19 wk with either 2.0 micrograms of 25-hydroxyvitamin D3, 2.0 micrograms of 24,24-difluoro-25-hydroxy-vitamin D3, 0.4 micrograms of 1,25-dihydroxyvitamin D3, 2.0 micrograms of 24,25-dihydroxyvitamin D3, 0.4 micrograms of 1,25-dihydroxyvitamin D3 plus 2.0 micrograms of 24,25-dihydroxyvitamin D3, or vehicle only. Normal embryonic development was found in eggs from hens given 25-hydroxyvitamin D3 or 24,24-difluoro-25-hydroxyvitamin D3, whereas embryos from hens given 1,25-dihydroxyvitamin D3, 24,25-dihydroxyvitamin D3, or their combination were abnormal and failed to hatch. Embryos from hens fed 1,25-dihydroxyvitamin D3 and/or 24,25-dihydroxyvitamin D3 had vitamin D deficiency: low bone ash, low plasma calcium, low total body calcium, and extremely high plasma phosphorus. Because the shell is the major source of calcium for the developing embryo, calcium transport from the shell to the embryos across the chorioallantoic membrane apparently fails, giving rise to the observed defects in embryonic development.

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