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

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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Dietary Calcium and 1,25-Dihydroxyvitamin D3 Regulate Transcription of Calcium Transporter Genes in Calbindin-D9k Knockout Mice

Journal of Reproduction and Development ◽

10.1262/jrd.20139 ◽

2009 ◽

Vol 55 (2) ◽

pp. 137-142 ◽

Cited By ~ 22

Author(s):

Sang-Hwan KO ◽

Geun-Shik LEE ◽

Thuy T. B. VO ◽

Eui-Man JUNG ◽

Kyung-Chul CHOI ◽

...

Keyword(s):

Knockout Mice ◽

Dietary Calcium ◽

Dihydroxyvitamin D3 ◽

1,25 Dihydroxyvitamin D3 ◽

Calbindin D9k ◽

Calcium Transporter

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

Vitamin D ◽

10.1515/9783110846713.598 ◽

1988 ◽

pp. 598-599

Keyword(s):

Dihydroxyvitamin D3 ◽

1,25 Dihydroxyvitamin D3 ◽

Calbindin D9k

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Duodenal Expression of 25 Hydroxyvitamin D3-1α-hydroxylase Is Higher in Adolescents Than in Children and Adults

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2015-1483 ◽

2015 ◽

Vol 100 (10) ◽

pp. 3668-3675 ◽

Cited By ~ 7

Author(s):

Aneta Gawlik ◽

Vardit Gepstein ◽

Nimrod Rozen ◽

Aviva Dahan ◽

Dafna Ben-Yosef ◽

...

Keyword(s):

Mrna Expression ◽

Calcium Absorption ◽

Maximum Velocity ◽

Dietary Calcium ◽

Maximum Activity ◽

Metabolic Adaptation ◽

Dihydroxyvitamin D3 ◽

Adolescents And Adults ◽

Igf1r Inhibitor ◽

25 Hydroxy Vitamin D

Context: Puberty is associated with increased dietary calcium absorption. However, little is known about the metabolic adaptations that enhance calcium absorption during puberty. Objectives: To investigate duodenal 25-hydroxy vitamin D-1α-hydroxylase (CYP 27B1) mRNA expression and duodenal 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) production in children, adolescents, and adults. Design and Methods: CYP27B1and IGF1 mRNA expression and 1,25(OH)2D3 production were determined in duodenal biopsies. CYP27B1 expression was also determined after IGF1R inhibitor treatment of human and mice duodenal explants. mRNA expression was determined by RT-PCR, and CYP27B1 activity was determined by incubating duodenal explants with 25(OH)D3 and measuring 1,25(OH)2D3 production by radioimmunoassay. Results: CYP27B1 mRNA expression was 13.7 and 10.4 times higher in biopsies from adolescents compared to adults and children, respectively. IGF1 mRNA expression was 30% and 45% higher in explants from adolescents and children, respectively, compared to adults. Inhibition of IGF1 receptor activity decreased CYP27B1expression in explants from both mice (85%) and humans (24%). 1,25(OH)2D3 production reached a maximum velocity of 768 ± 268 pmol/l/mg protein at 748.8 nmol/l of 25(OH)D3 in children and adolescents, whereas the maximum velocity was 86.4 ± 43.2 pmol/l/mg protein in adults. The substrate concentration at which the enzyme shows half of its maximum activity was similar in all groups, ranging between 624 and 837 nmol/L of 25(OH)D3. Conclusions: Increased CYP27B1 expression and local duodenal 1,25(OH)2D3 production during puberty may be a metabolic adaptation that promotes dietary calcium absorption. IGF1, a major factor in skeletal growth, is also involved in the modulation of CYP27B1 expression in the gut and may increase calcium supply for the growing bone.

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