ELEVATED 1,25-DIHYDROXYVITAMIN D3 AND INTESTINAL CALBINDIN-D9K LEVELS IN THE OSTEOPETROTIC TOOTHLESS RAT.

The toothless (tl) rat is a nonlethal osteopetrotic mutation characterized by systemic skeletal sclerosis, growth plate morphology suggestive of rickets, and morphological evidence of reduced osteoclastic bone resorption. Vitamin D metabolites, serum calcium and phosphorus levels, and the developmental appearance of vitamin D-dependent intestinal calcium binding protein (calbindin-D9k) was studied in normal and mutant rats of tl stock from 7 to 35 days of age. 1,25-Dihydroxyvitamin D3 [1,25-(OH)2D3] was found to be significantly elevated in mutant animals by 7 days of age (71 +/- 9 pM, tl/tl vs. 24 +/- 8 pM, +/?) and continued to increase to a peak of 428 pM at the time of weaning. This was 240% higher than normals at this period. The elevated levels of 1,25-(OH)2D3 stimulated a significant and precocious appearance of intestinal calbindin-D9k in mutants, beginning by 14 days of age and reaching their peak levels at 21 days postpartum (25.6 +/- 1.7 micrograms/mg protein, tl/tl vs. 16.4 +/- 1.5 micrograms/mg protein, +/?). The cause of the elevated circulating levels of 1,25-(OH)2D3 in tl rats is unknown but may be due to the low serum phosphorus levels present in these animals.

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Calcium Transporter 1 and Epithelial Calcium Channel Messenger Ribonucleic Acid Are Differentially Regulated by 1,25 Dihydroxyvitamin D3 in the Intestine and Kidney of Mice

Endocrinology ◽

10.1210/en.2003-0314 ◽

2003 ◽

Vol 144 (9) ◽

pp. 3885-3894 ◽

Cited By ~ 177

Author(s):

Yurong Song ◽

Xiaorong Peng ◽

Angela Porta ◽

Hitomi Takanaga ◽

Ji-Bin Peng ◽

...

Keyword(s):

Calcium Channel ◽

Mrna Expression ◽

Dietary Calcium ◽

Mrna Levels ◽

Dihydroxyvitamin D3 ◽

Messenger Ribonucleic Acid ◽

1,25 Dihydroxyvitamin D3 ◽

Calbindin D9k ◽

Intestinal Ca Absorption ◽

Calcium Transporter

Abstract We examined the expression of calcium transporter 1 (CaT1) and epithelial calcium channel (ECaC) mRNA in the duodenum and kidney of mice. Intestinal CaT1 mRNA level increased 30-fold at weaning, coincident with the induction of calbindin-D9k expression. In contrast, renal CaT1 and ECaC mRNA expression was equal until weaning when ECaC mRNA is induced and CaT1 mRNA levels fall 70%. Long- and short-term adaptation to changes in dietary calcium (Ca) level and 1,25 dihydroxyvitamin D3 [1,25(OH)2D3] injection strongly regulated duodenal calbindin D9k and CaT1 mRNA. Following a single dose of 1,25(OH)2D3, induction of CaT1 mRNA occurred rapidly (within 3 h, peak at 6 h of 9.6 ± 0.8-fold) and preceded the induction of intestinal Ca absorption (significantly increased at 6 h, peak at 9 h). Neither renal CaT1 nor ECaC mRNA were strongly regulated by dietary calcium level or 1,25(OH)2D3 injection. Our data indicate that CaT1 and ECaC mRNA levels are differentially regulated by 1,25(OH)2D3 in kidney and intestine and that there may be a specialized role for CaT1 in kidney in fetal and neonatal development. The rapid induction of intestinal CaT1 mRNA expression by 1,25(OH)2D3, and the marked induction at weaning, suggest that CaT1 is critical for 1,25(OH)2D3-mediated intestinal Ca absorption.

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