Hormonal regulation of glutathione S-transferase expression in co-culturedadult rat hepatocytes

Glutathione S-transferases (GSTs) are subject to regulation by thyroid and sex hormones and by GH. We have used an in vitro experimental system compri sing adult rat hepatocytes co-cultured with rat liver epithelial cells of p rimitive biliary origin, to distinguish between direct and indirect effects of various hormones on GSTs; to identify the GST subunits affected by indi vidual hormones; and to investigate the level at which the hormones act. Tr i-iodothyronine (T-3), thyroxine (T-4) and 17 beta-oestradiol (OE2) reduced GST activities, whereas testosterone, dihydrotestosterone, and human growt h hormone (hGH) had little effect on total GST activity. HPLC separation of the various GST subunits revealed that T-3 and T-4 reduced total GST conte nt, in particular the abundance of subunits M1 and M2. The amount of the Pi -class subunit P1 was reduced by OE2. Treatment of the co-cultured cells wi th this hormone altered the GST subunit profile to one that is more similar to that observed in freshly isolated hepatocytes. Analysis of mRNAs demons trated that some of the hormones act at a pre-translational level, whereas others act at a translational or post-translational level to regulate the e xpression of various GST subunits.