High sensitivity of rat hepatic vitamin D3-25 hydroxylase CYP27A to 1,25-dihydroxyvitamin D3 administration

Abstract

CYP27A is considered the main vitamin D3 (D3)-25 hydroxylase in humans. Our purpose was to evaluate the effect of the D3 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 D3, 25OHD3, or 1,25(OH)2D3. 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 D3 nor 25OHD3 influenced CYP27A mRNA levels. However, 1,25(OH)2D3 repletion led to a 60% decrease in CYP27A mRNA, which was accompanied by a 46% decrease in mitochondrial D3-25 hydroxylase activity. The effect of 1,25(OH)2D3 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 D3 nutritional status but is transcriptionally regulated by 1,25(OH)2D3 exposure.