title: Regulation of messenger ribonucleic acid expression of 1 alpha,25-dihydroxyvitamin D3-24-hydroxylase in rat osteoblasts.
abstract: 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.
authors.affiliation: Department of Biochemistry, School of Dentistry, Showa University, Tokyo, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Nishimura
authors.forename: T
authors.initials: T
authors.lastname: Shinki
authors.forename: C H
authors.initials: CH
authors.lastname: Jin
authors.forename: Y
authors.initials: Y
authors.lastname: Ohyama
authors.forename: M
authors.initials: M
authors.lastname: Noshiro
authors.forename: K
authors.initials: K
authors.lastname: Okuda
authors.forename: T
authors.initials: T
authors.lastname: Suda
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D002117:Calcitriol / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D000242:Cyclic AMP / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics* / Q000378:metabolism; D015232:Dinoprostone / Q000494:pharmacology; D008297:Male; D010006:Osteoblasts / Q000378:metabolism*; D010281:Parathyroid Hormone / Q000378:metabolism / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D018167:Receptors, Calcitriol / Q000235:genetics / Q000378:metabolism; D013250:Steroid Hydroxylases / Q000235:genetics* / Q000378:metabolism; D013997:Time Factors; D065668:Vitamin D3 24-Hydroxylase
chemical_list: D010281:Parathyroid Hormone; D012333:RNA, Messenger; D018167:Receptors, Calcitriol; D003577:Cytochrome P-450 Enzyme System; D000242:Cyclic AMP; D013250:Steroid Hydroxylases; D065668:Vitamin D3 24-Hydroxylase; D000262:Adenylyl Cyclases; D002117:Calcitriol; D015232:Dinoprostone; D002118:Calcium