Differential time course of induction of 1alpha,25-dihydroxyvitamin D3-24-hydroxylase mRNA expression in rats by 1alpha,25-dihydroxyvitamin D3 and its analogs.
In order to investigate the in vivo mechanisms of target gene activation by vitamin D3 analogs, we compared the effects of two vitamin D3 analogs, 22-oxa-1alpha,25-(OH)2D3 (OCT) and 2beta (3-hydroxypropoxy) -1alpha,25-(OH)2D3 (ED-71) with that of 1alpha,25-(OH)2D3 on 1alpha,25-(OH)2D3 -24-hydroxylase[24(OH)ase] mRNA expression in the kidney and intestine of normal rats. In these experiments, all three compounds induced 24(OH)ase mRNA, but the time course of induction for each respective treatment was clearly different. OCT caused the most rapid onset of increased 24(OH)ase mRNA expression and its subsequent return to pre-injection levels. In marked contrast, ED-71 was the slowest to increase expression which was prolonged over that observed with the other compounds tested. These differences probably relate to the pharmacokinetic properties of these analogs, which are mainly generated by the affinity of analogs for the vitamin D-binding protein(DBP).
Furuichi
T
T
Fuji-Gotemba Research Laboratory, Chugai Pharmaceutical Co. Ltd., Shizuoka, Japan.
Kawata
S
S
Asoh
Y
Y
Kumaki
K
K
Ohyama
Y
Y
D000818:Animals; D002117:Calcitriol / Q000031:analogs & derivatives / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D007422:Intestines / Q000201:enzymology; D007668:Kidney / Q000201:enzymology; D008297:Male; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D013250:Steroid Hydroxylases / Q000235:genetics*; D013997:Time Factors; D015533:Transcriptional Activation; D014807:Vitamin D / Q000031:analogs & derivatives; D065668:Vitamin D3 24-Hydroxylase
D012333:RNA, Messenger; D014807:Vitamin D; D003577:Cytochrome P-450 Enzyme System; D013250:Steroid Hydroxylases; D065668:Vitamin D3 24-Hydroxylase; D002117:Calcitriol; C547512:eldecalcitol; C051883:maxacalcitol