High sensitivity of rat hepatic vitamin D3-25 hydroxylase CYP27A to 1,25-dihydroxyvitamin D3 administration.
CYP27A is considered the main vitamin D(3) (D(3))-25 hydroxylase in humans. Our purpose was to evaluate the effect of the D(3) nutritional and hormonal status on hepatic CYP27A mRNA, cellular distribution, transcription rate, and enzyme activity. Studies were carried out in normal and in D-depleted rats supplemented with D(3), 25OHD(3), or 1,25(OH)(2)D(3). CYP27A exhibited a significant gender difference and was observed throughout the hepatic acinus not only in hepatocytes but also in sinusoidal endothelial, stellate, and Kupffer cells. Neither D(3) nor 25OHD(3) influenced CYP27A mRNA levels. However, 1,25(OH)(2)D(3) repletion led to a 60% decrease in CYP27A mRNA, which was accompanied by a 46% decrease in mitochondrial D(3)-25 hydroxylase activity. The effect of 1,25(OH)(2)D(3) was mediated by a significant decrease in CYP27A transcription, whereas its mRNA half-life remained unchanged. Our data indicate that CYP27A is present in hepatic parenchymal and sinusoidal cells and that the gene transcript is not influenced by the D(3) nutritional status but is transcriptionally regulated by 1,25(OH)(2)D(3) exposure.
Theodoropoulos
Catherine
C
Centre de recherche, Hôpital Saint-Luc, Centre Hospitalier de l'Université de Montréal, Département de Pharmacologie, Faculté de médecine, Université de Montréal, Quebec, Canada H2X 1P1.
Demers
Christian
C
Petit
Jean-Luc
JL
Gascon-Barre
Marielle
M
D000818:Animals; D002112:Calcifediol / Q000097:blood / Q000494:pharmacology; D002117:Calcitriol / Q000097:blood / Q000494:pharmacology*; D002118:Calcium / Q000097:blood; D002762:Cholecalciferol / Q000494:pharmacology; D053493:Cholestanetriol 26-Monooxygenase; D004730:Endothelium, Vascular / Q000201:enzymology; D005260:Female; D006207:Half-Life; D022781:Hepatocytes / Q000201:enzymology; D007700:Kinetics; D007728:Kupffer Cells / Q000201:enzymology; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D008930:Mitochondria, Liver / Q000201:enzymology; D009752:Nutritional Status; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D012727:Sex Characteristics; D013250:Steroid Hydroxylases / Q000235:genetics* / Q000378:metabolism*; D014158:Transcription, Genetic
D012333:RNA, Messenger; D002762:Cholecalciferol; D013250:Steroid Hydroxylases; D053493:Cholestanetriol 26-Monooxygenase; D002117:Calcitriol; D002112:Calcifediol; D002118:Calcium