T. Shinki et al., Calcitonin is a major regulator for the expression of renal 25-hydroxyvitamin D-3-1 alpha-hydroxylase gene in normocalcemic rats, P NAS US, 96(14), 1999, pp. 8253-8258
Citations number
38
Categorie Soggetti
Multidisciplinary
Journal title
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Regulation of vitamin D metabolism has long been examined by using vitamin
D-deficient hypocalcemic animals. We previously reported that, in a rat mod
el of chronic hyperparathyroidism, expression of 25-hydroxyvitamin D-3-1 al
pha-hydroxylase (CYP27B1) mRNA was markedly increased in renal proximal con
voluted tubules, It is believed that the major regulator for the expression
of renal CYP27B1 is parathyroid hormone (PTH). However, in the normocalcem
ic state, the mechanism to regulate the renal CYP27B1 gene could be differe
nt, since plasma levels of PTH are very low. In the present study, the effe
ct of PTH and calcitonin (CT) on the expression of renal CYP27B1 mRNA was i
nvestigated in normocalcemic sham-operated rats and normocalcemic thyropara
thyroidectomized (TPTX) rats generated by either PTH or CaCl2 infusion. A s
ingle injection of CT dose-dependently decreased the expression of vitamin
D receptor mRNA in the kidney of normocalcemic sham-TPTX rats. Concomitantl
y, CT greatly increased the expression of CYP27B1 mRNA in the kidney of nor
mocalcemic sham-TPTX rats. CT also increased the expression of CYP27B1 mRNA
in the kidney of normocalcemic TPTX rats. Conversion of serum [H-3]1 alpha
,25(OH)(2)D-3 from 25-hydroxy[H-3]vitamin D-3 in vivo was also greatly incr
eased by the injection of CT into sham-TPTX rats and normocalcemic TPTX rat
s, 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-re
plete sham-TPTX rats and hypocalcemic TPTX rats. PTH increased the expressi
on 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 1 alpha,25(OH)(2)D-3 under normocalcemic physiological conditions,
at least in rats.