Triiodothyronine downregulates the periportal expression of alpha class glutathione S-transferase in rat liver

Most drug-metabolizing phase I and phase II enzymes, including the glutathi one S-transferases (GST), exhibit a zonated expression in the liver, with l ower expression in the upstream, periportal region. To elucidate the involv ement of pituitary-dependent hormones in this zonation, the effect of hypop hysectomy and 3,3',5-triiodo-L-thyronine (T-3) on the distribution of GST w as studied in rats. Hypophysectomy increased total GST activity both in the periportal and perivenous liver region. Subsequent T-3 treatment counterac ted this effect in the perivenous zone. However, analysis for either mu cla ss M1/M2-specific (1,2-dichloro-4-nitrobenzene) or alpha class A1/A2-specif ic (7-chloro-4-nitrobenzo-2-oxa-1,3-diazole) GST activity revealed that T-3 treatment did not significantly affect the perivenous activity of these GS T classes. In contrast, T-3 was found to significantly counteract the incre ase of a class GST activity caused by hypophysectomy in the periportal zone . To establish whether this effect was T-3-specific, hepatocytes were isola ted from either the periportal and perivenous zone by digitonin/collagenase perfusion and cultured either as pyruvate-supplemented monolayer or as co- culture with rat liver epithelial cells. Only in the latter it was found th at T-3 suppressed the A1/ A2-specific GST activity and alpha class proteins predominantly in periportal cells. The data demonstrate that T-3 is an imp ortant factor responsible for the low expression of alpha GST in the peripo rtal region. T-3 may be involved in the periportal downregulation of other phase I and II enzymes as well. (C) 2001 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.