Regulation of human hepatic hydroxysteroid sulfotransferase gene expression by the peroxisome proliferatoractivated receptor alpha transcription

Human hydroxysteroid sulfotransferase or (HUMAN)SULT2A1 catalyzes the sulfonation of procarcinogen xenobiotics, hy-droxysteroids, and bile acids and plays a dynamic role in hepatic cholesterol homeostasis. The treatment of primary cultured human hepatocytes with a peroxisome proliferator-activated receptor (PPAR)-activating concentration of cip-rofibrate (104 M) increased (HUMAN)SULT2A1 mRNA, immu-noreactive protein, and enzymatic activity levels by 2-fold. By contrast, expression of (RAT)SULT2A3, the rat counterpart to (HUMAN)SULT2A1, was induced by treatment of primary he-patocyte cultures with an activator of the pregnane X receptor, but not PPAR. In HepG2 cells, transient transfection analyses of luciferase reporter constructs containing upstream regions of the (HUMAN)SULT2A1 gene implicated a candidate peroxi