Regulation of messenger ribonucleic acid expression of 1 alpha,25-dihydroxyvitamin D3-24-hydroxylase in rat osteoblasts

Endocrinology. 1994 Apr;134(4):1794-9. doi: 10.1210/endo.134.4.8137744.


We have reported that PTH inhibits 25-hydroxyvitamin D3-24-hydroxylase messenger RNA (mRNA) expression induced by 1 alpha,25-dihydroxyvitamin D3 [1 alpha, 25-(OH)2D3] in rat kidney but not intestine. In the present study, we examined whether the suppression of 24-hydroxylase mRNA expression by PTH occurs commonly in tissues and cells which have PTH receptors. Administration of 1 alpha, 25-(OH)2D3 into rats fed a synthetic vitamin D-repleted diet containing adequate calcium greatly increased serum levels of calcium and 1 alpha, 25-(OH)2D3. Also, there was a 4-fold increase in bone 24-hydroxylase activity in response to 1 alpha, 25-(OH)2D3 administration. In rats fed a low calcium diet, renal 24-hydroxylase activity was suppressed probably due to secondary hyperparathyroidism. In contrast, the low calcium feeding did not suppress bone 24-hydroxylase activity. The expression of 24-hydroxylase mRNA in rat osteoblastic C-26 and C-11 cells was similar and attained maximal levels 24 h after cells were incubated with 10(-8) M 1 alpha, 25-(OH)2D3. Induction of 24-hydroxylase mRNA expression by 1 alpha, 25-(OH)2D3 was much greater and earlier in immature C-26 cells than mature C-11 cells. Simultaneous addition of PTH, prostaglandin E2, or cAMP together with 1 alpha, 25-(OH)2D3 did not down-regulate mRNA expression of 24-hydroxylase induced by the vitamin in both C-26 and C-11 cells. Of the three osteoblastic cells (C-26, C-20, and C-11) examined, C-26 cells showed the least mRNA expression of vitamin D receptors, in spite of the highest expression of 24-hydroxylase mRNA. These results suggest that unlike in the kidney, bone 24-hydroxylase mRNA expression is not down-regulated by PTH despite of the presence of PTH receptors. They also suggest that the degree of the induction of 24-hydroxylase mRNA by 1 alpha, 25-(OH)2D3 is not explained simply by the vitamin D receptors content.

MeSH terms

  • Adenylyl Cyclases / metabolism
  • Animals
  • Calcitriol / pharmacology
  • Calcium / metabolism
  • Cell Line
  • Cyclic AMP / pharmacology
  • Cytochrome P-450 Enzyme System / genetics*
  • Cytochrome P-450 Enzyme System / metabolism
  • Dinoprostone / pharmacology
  • Male
  • Osteoblasts / metabolism*
  • Parathyroid Hormone / metabolism
  • Parathyroid Hormone / pharmacology
  • RNA, Messenger / metabolism*
  • Rats
  • Rats, Inbred Strains
  • Receptors, Calcitriol / genetics
  • Receptors, Calcitriol / metabolism
  • Steroid Hydroxylases / genetics*
  • Steroid Hydroxylases / metabolism
  • Time Factors
  • Vitamin D3 24-Hydroxylase


  • Parathyroid Hormone
  • RNA, Messenger
  • Receptors, Calcitriol
  • Cytochrome P-450 Enzyme System
  • Cyclic AMP
  • Steroid Hydroxylases
  • Vitamin D3 24-Hydroxylase
  • Adenylyl Cyclases
  • Calcitriol
  • Dinoprostone
  • Calcium