title: Triiodothyronine downregulates the periportal expression of alpha class glutathione S-transferase in rat liver.
abstract: Most drug-metabolizing phase I and phase II enzymes, including the glutathione S-transferases (GST), exhibit a zonated expression in the liver, with lower expression in the upstream, periportal region. To elucidate the involvement of pituitary-dependent hormones in this zonation, the effect of hypophysectomy and 3,3',5-triiodo-L-thyronine (T3) on the distribution of GST was studied in rats. Hypophysectomy increased total GST activity both in the periportal and perivenous liver region. Subsequent T3 treatment counteracted this effect in the perivenous zone. However, analysis for either mu class M1/M2-specific (1,2-dichloro-4-nitrobenzene) or alpha class A1/A2-specific (7-chloro-4-nitrobenzo-2-oxa-1,3-diazole) GST activity revealed that T3 treatment did not significantly affect the perivenous activity of these GST classes. In contrast, T3 was found to significantly counteract the increase of alpha class GST activity caused by hypophysectomy in the periportal zone. To establish whether this effect was T3-specific, hepatocytes were isolated 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 that T3 suppressed the A1/A2-specific GST activity and alpha class proteins predominantly in periportal cells. The data demonstrate that T3 is an important factor responsible for the low expression of alpha GST in the periportal region. T3 may be involved in the periportal downregulation of other phase I and II enzymes as well.
authors.affiliation: Department of Toxicology, Vrije Universiteit Brussel, Belgium. tamaravh@vub.vub.ac.be
authors.forename: T
authors.initials: T
authors.lastname: Vanhaecke
authors.forename: K O
authors.initials: KO
authors.lastname: Lindros
authors.forename: T
authors.initials: T
authors.lastname: Oinonen
authors.forename: A
authors.initials: A
authors.lastname: Vercruysse
authors.forename: V
authors.initials: V
authors.lastname: Rogiers
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects; D005982:Glutathione Transferase / Q000737:chemistry / Q000145:classification / Q000378:metabolism*; D022781:Hepatocytes / Q000187:drug effects / Q000201:enzymology; D007016:Hypophysectomy; D007527:Isoenzymes / Q000737:chemistry / Q000145:classification / Q000378:metabolism*; D008099:Liver / Q000187:drug effects* / Q000201:enzymology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution; D014284:Triiodothyronine / Q000494:pharmacology*
chemical_list: D007527:Isoenzymes; D014284:Triiodothyronine; D005982:Glutathione Transferase; C119995:glutathione S-transferase alpha