Consequences of vitamin D receptor regulation for the 1,25-dihydroxyvitamin D3-induced 24-hydroxylase activity in osteoblast-like cells: Initiation of the C24-oxidation pathway

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.

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Vitamin D receptor in IMR-90 human fibroblasts and antiproliferative effect of 1,25-dihydroxyvitamin D3

IUBMB Life ◽

10.1080/15216549700205011 ◽

1997 ◽

Vol 43 (6) ◽

pp. 1173-1181 ◽

Cited By ~ 3

Author(s):

M. Stio ◽

A. Celli ◽

B. Lunghi ◽

G. Raugei ◽

A. Modesti ◽

...

Keyword(s):

Vitamin D ◽

Vitamin D Receptor ◽

Human Fibroblasts ◽

Antiproliferative Effect ◽

Dihydroxyvitamin D3 ◽

1,25 Dihydroxyvitamin D3

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1,25-Dihydroxyvitamin D3-inducible catabolism of vitamin D metabolites in mouse intestine

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1990.258.4.g557 ◽

1990 ◽

Vol 258 (4) ◽

pp. G557-G563 ◽

Cited By ~ 1

Author(s):

M. Tomon ◽

H. S. Tenenhouse ◽

G. Jones

Keyword(s):

Vitamin D ◽

Enzyme Activity ◽

Actinomycin D ◽

Vitamin D Metabolites ◽

Catabolic Pathway ◽

Dihydroxyvitamin D3 ◽

Oxidation Pathway ◽

1,25 Dihydroxyvitamin D3 ◽

Mouse Intestine ◽

Alpha Amanitin

The 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]-inducible C-24 oxidation pathway is a major catabolic pathway for vitamin D metabolites in target tissues. Using intestinal homogenates derived from 1,25(OH)2D3-treated mice, we examined the time course of induction, the intestinal localization and kinetics of induced enzyme activity, as well as the sensitivity of induction to transcriptional inhibitors actinomycin D and alpha-amanitin. 24-Hydroxylation of 500 nM 3H-labeled 25-hydroxyvitamin D3 [25(OH)D3] and 50 nM 3H-labeled 1,25(OH)2D3 by duodenal homogenates was detected 1 h after 1,25(OH)2D3 treatment; C-24 oxidation products of 25(OH)D3 and 1,25(OH)2D3 peaked at approximately 6 h and remained elevated for 17 h. Induced enzyme activity was localized to the mitochondrial fraction, was highest in duodenum, and was also detected in jejunum, ileum, and colon. The apparent Michaelis constant of the induced duodenal enzyme for 25(OH)D3 was 451 nM and for 1,25(OH)2D3 was 14 nM. Induction of intestinal catabolic activity was inhibited by prior treatment of 1,25(OH)2D3-injected mice with either actinomycin D or alpha-amanitin. The characteristics of the 1,25(OH)2D3-inducible C-24 oxidation pathway in the intestine resembled that of the kidney. However, the catabolic pathway was constitutively expressed only in the kidney. We conclude that 1,25(OH)2D3-inducible degradation of vitamin D metabolites occurs throughout the length of mouse intestine and can be prevented by transcriptional inhibitors, suggesting that mRNA synthesis is required for the induction process.

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