Hormonal regulation of glutathione S-transferase expression in co-cultured adult 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 comprising adult rat hepatocytes co-cultured with rat liver epithelial cells of primitive biliary origin, to distinguish between direct and indirect effects of various hormones on GSTs; to identify the GST subunits affected by individual hormones; and to investigate the level at which the hormones act. Tri-iodothyronine (T3), thyroxine (T4) and 17beta-oestradiol (OE2) reduced GST activities, whereas testosterone, dihydrotestosterone, and human growth hormone (hGH) had little effect on total GST activity. HPLC separation of the various GST subunits revealed that T3 and T4 reduced total GST content, 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 with this hormone altered the GST subunit profile to one that is more similar to that observed in freshly isolated hepatocytes. Analysis of mRNAs demonstrated that some of the hormones act at a pre-translational level, whereas others act at a translational or post-translational level to regulate the expression of various GST subunits.
Coecke
S
S
Department of Toxicology, Vrije Universiteit Brussel, Laarbeeklaan 103, B-1090 Brussels, Belgium.
Vanhaecke
T
T
Foriers
A
A
Phillips
I R
IR
Vercruysse
A
A
Shephard
E A
EA
Rogiers
V
V
D000818:Animals; D015152:Blotting, Northern; D002478:Cells, Cultured; D018920:Coculture Techniques; D013196:Dihydrotestosterone / Q000494:pharmacology; D004847:Epithelial Cells / Q000201:enzymology; D004958:Estradiol / Q000494:pharmacology; D005786:Gene Expression Regulation; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism*; D012739:Gonadal Steroid Hormones / Q000494:pharmacology*; D022781:Hepatocytes / Q000187:drug effects / Q000201:enzymology*; D019382:Human Growth Hormone / Q000494:pharmacology*; D007527:Isoenzymes / Q000378:metabolism*; D008297:Male; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013739:Testosterone / Q000494:pharmacology; D013963:Thyroid Hormones / Q000494:pharmacology*; D013974:Thyroxine / Q000494:pharmacology; D014284:Triiodothyronine / Q000494:pharmacology
D012739:Gonadal Steroid Hormones; D007527:Isoenzymes; D012333:RNA, Messenger; D013963:Thyroid Hormones; D014284:Triiodothyronine; D013196:Dihydrotestosterone; D019382:Human Growth Hormone; D013739:Testosterone; D004958:Estradiol; D005982:Glutathione Transferase; D013974:Thyroxine