| Abstrakt: |
CYP27A is considered the main vitamin D[sub 3] (D[sub 3])-25 hydroxylase in humans. Our purpose was to evaluate the effect of the D[sub 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[sub 3], 250HD[sub 3], or 1,25(OH)[sub 2]D[sub 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[sub 3] nor 25OHD[sub 3] influenced CYP27A mRNA levels. However, 1,25(OH)[sub 2]D[sub 3] repletion led to a 60% decrease in CYP27A mRNA, which was accompanied by a 46% decrease in mitochondrial D[sub 3]-25 hydroxylase activity. The effect of 1,25(OH)[sub 2]D[sub 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[sub 3] nutritional status but is transcriptionally regulated by 1,25(OH)[sub 2]D[sub 3] exposure. [ABSTRACT FROM AUTHOR] |
