T. Vanhaecke et al., Triiodothyronine downregulates the periportal expression of alpha class glutathione S-transferase in rat liver, FEBS LETTER, 487(3), 2001, pp. 356-360
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.