The liver is generally considered negative for the vitamin D nuclear receptor (VDRn), even though several studies have shown significant effects of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) on liver cell physiology. The low abundance of VDRn in the liver led us to propose that hepatocytes (the largest hepatic cell population) were most likely negative for the receptor, whereas the small hepatic sinusoidal and ductular cell populations that contain cell types known to express VDRn in other tissues should express the receptor. Using freshly isolated cells from normal livers as well as biliary and epithelial hepatic cell lines, our data show that the human, rat, and mouse hepatocytes express very low VDRn messenger RNA (mRNA) and protein levels. In contrast, sinusoidal endothelial, Kupffer, and stellate cells of normal rat livers as well as the mouse biliary cell line BDC and rat hepatic neonatal epithelial SD6 cells clearly expressed both VDRn mRNA and protein. In addition, specimens of human hepatocarcinoma as well as intrahepatic colon adenocarcinoma metastases were also found to express the VDRn gene transcript. Kupffer, stellate, and endothelial cells responded to 1,25(OH)2D3 by a significant increase in the CYP24, indicating that the VDRn is fully functional in these cells. In conclusion, selective hepatic cell populations are targets for the vitamin D endocrine/paracrine/intracrine system.
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