Calcitonin Is a Major Regulator for the Expression of Renal 25-Hydroxyvitamin D3-1α -Hydroxylase Gene in Normocalcemic Rats

Regulation of vitamin D metabolism has long been examined by using vitamin D-deficient hypocalcemic animals. We previously reported that, in a rat model of chronic hyperparathyroidism, expression of 25-hydroxyvitamin D3-1α -hydroxylase (CYP27B1) mRNA was markedly increased in renal proximal convolut...

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Published inProceedings of the National Academy of Sciences - PNAS Vol. 96; no. 14; pp. 8253 - 8258
Main Authors Shinki, Toshimasa, Ueno, Yutaka, DeLuca, Hector F., Suda, Tatsuo
Format Journal Article
LanguageEnglish
Published National Academy of Sciences of the United States of America 06.07.1999
National Acad Sciences
The National Academy of Sciences
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Summary:Regulation of vitamin D metabolism has long been examined by using vitamin D-deficient hypocalcemic animals. We previously reported that, in a rat model of chronic hyperparathyroidism, expression of 25-hydroxyvitamin D3-1α -hydroxylase (CYP27B1) mRNA was markedly increased in renal proximal convoluted tubules. It is believed that the major regulator for the expression of renal CYP27B1 is parathyroid hormone (PTH). However, in the normocalcemic state, the mechanism to regulate the renal CYP27B1 gene could be different, since plasma levels of PTH are very low. In the present study, the effect of PTH and calcitonin (CT) on the expression of renal CYP27B1 mRNA was investigated in normocalcemic sham-operated rats and normocalcemic thyroparathyroidectomized (TPTX) rats generated by either PTH or CaCl2 infusion. A single injection of CT dose-dependently decreased the expression of vitamin D receptor mRNA in the kidney of normocalcemic sham-TPTX rats. Concomitantly, CT greatly increased the expression of CYP27B1 mRNA in the kidney of normocalcemic sham-TPTX rats. CT also increased the expression of CYP27B1 mRNA in the kidney of normocalcemic TPTX rats. Conversion of serum [3H]1α,25(OH)2D3 from 25-hydroxy[3H]vitamin D3 in vivo was also greatly increased by the injection of CT into sham-TPTX rats and normocalcemic TPTX rats, but not into hypocalcemic TPTX rats. In contrast, administration of PTH did not induce the expression of CYP27B1 mRNA in the kidney of vitamin D-replete sham-TPTX rats and hypocalcemic TPTX rats. PTH increased the expression of renal CYP27B1 mRNA only in vitamin D-deficient hypocalcemic TPTX rats. These results suggest that CT plays an important role in the maintenance of serum 1α,25(OH)2D3 under normocalcemic physiological conditions, at least in rats.
Bibliography:To whom reprint requests should be addressed at: Department of Biochemistry, School of Dentistry, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan. e-mail: shinki@dent.showa-u.ac.jp.
Contributed by Hector F. DeLuca
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.96.14.8253