Parathyroid hormone and 1,25-dihydroxyvitamin D synergistically induce the 1,25-dihydroxyvitamin D-24-hydroxylase in rat UMR-106 osteoblast-like cells.
We have studied the effect of parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D3 (1,25(OH)2D) on the expression of the 1,25-dihydroxyvitamin D-24-hydroxylase (24-hydroxylase) in rat UMR-106 osteoblastic cells. 1,25(OH)2D (10(-7) M) alone produced a gradual increase in mRNA levels of the 24-hydroxylase cytochrome P450 component (P450cc24) during 12 hours of incubation. Rat PTH 1-34 (250 nM) in the presence of 1,25(OH)2D further increased P450cc24 mRNA levels 7-10 fold after 3 hours. PTH alone had no significant effect. The action of PTH was mimicked by forskolin but not by phorbol ester. The 24-hydroxylase enzymatic activity in UMR cells was increased over 5-fold by PTH and 1,25(OH)2D together compared to 1,25(OH)2D alone after 6 hours. This synergistic regulation of the 24-hydroxylase in bone cells is in contrast to the regulation in the kidney, where PTH and 1,25(OH)2D have opposite effects on 24-hydroxylase expression.
Armbrecht
H J
HJ
Geriatric Research, Education, and Clinical Center, Veterans Affairs Medical Center, St. Louis, MO 63125.
Hodam
T L
TL
D000818:Animals; D002117:Calcitriol / Q000494:pharmacology*; D002460:Cell Line; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System; D004357:Drug Synergism; D004789:Enzyme Activation; D010006:Osteoblasts / Q000201:enzymology*; D010281:Parathyroid Hormone / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D013250:Steroid Hydroxylases / Q000096:biosynthesis* / Q000235:genetics; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D065668:Vitamin D3 24-Hydroxylase
D010281:Parathyroid Hormone; D012333:RNA, Messenger; D003577:Cytochrome P-450 Enzyme System; D013250:Steroid Hydroxylases; D065668:Vitamin D3 24-Hydroxylase; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D002117:Calcitriol; D013755:Tetradecanoylphorbol Acetate