Hepatic mRNA induction

Slc22/Organic Ion Transporter Family. Few studies have reported the induction of Slc22a genes by PXR activators. By using rat hepatoma RL-34 cells, cultured primary rat hepatocytes and animals, it was shown that PCN induced the expression of rat hepatic Octl (Slc22al) mRNA. Induction of Octl transporter activity was further demonstrated ex vivo by increased uptake of the prototypical substrate MPP+ into hepatocytes, which were isolated from PCN-treated rats, compared to cells, which were isolated from control animals and in vivo by an increase in biliary excretion of TEA in PCN-treated rats [130]. 

Single ip injection of 50 or 250 mg PCB 153/kg BW of juveniles 20-60 g BW livers examined after 4 weeks Dose-dependent induction of hepatic EROD activity, CYP1A protein, and CYP1A1 mRNA content 17... 

Cherrington NJ, Hartley DP, Li N, et al. Organ distribution of multidrug resistance proteins 1, 2, and 3 (Mrpl, 2, and 3) mRNA and hepatic induction of Mrp3 by constitutive androstane receptor activators in rats. J Pharmacol Exp Ther 2002 300 97-104. 

Induction of mRNAs for several other specific rat hepatic proteins by GH has also been demonstrated [81-83]. The effect could be demonstrated in vivo and in vitro and involved a relatively rapid induction with a 5-fold increase in mRNA levels within 4 h of the administration of GH, although synergism with cortisol (possibly and/or thyroxine) was necessary for a maximal response [83]. cDNAs corresponding to two of the induced proteins have been cloned [82,83] and found to have sequences homologous to those of a known family of serine protease inhibitors. One of these proteins was shown to be secreted as a heavily glycosylated serum protein, and to have potent anti-trypsin activity [83]. Regulation of the production of this protein by GH was shown to occur mainly at the transcriptional level [83]. 

The induction of hepatic tyrosine aminotransferase (TAT) mRNA and activity is a classical measure of corticosteroid-mediated pharmacogenomic effects. The TAT dynamics are modeled in a manner consistent with precursor-dependent models, where the stimulation function acts on the production rate of the precursor species ... 

Biochemical induction studies in rats and primary rat hepatocytes demonstrated that digitoxigenin monodigitoxoside UGT activity could be induced by glucocorticoids, which is consistent with induction of UGT activity via PXR [71], Similarly, hepatic UGT activity versus bilirubin, 1-naphthol, chloramphenicol, thyroxine, and trioodothyronine were induced, and mRNA levels of Ugtlal and la9 were more than 100% increased in mice following PCN treatment [86], By contrast, the PXR... 

MRP2 (ABCC2). The induction of rat hepatic Mrp2 expression by PXR and CAR activators has been demonstrated by several studies using hepatoma cell lines, primary hepatocytes, and animals. The rat hepatoma FAO cell line showed an increase in Mrp2 mRNA expression by treatment with PCN [99]. Primary cultures of rat hepatocytes also demonstrated induction of Mrp2 by treatment with the PXR... 

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