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Triiodothyronine downregulates the periportal expression of α class glutathione S ‐transferase in rat liver
Author(s) -
Vanhaecke T.,
Lindros K.O.,
Oin T.,
Vercruysse A.,
Rogiers V.
Publication year - 2001
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(00)02353-x
Subject(s) - endocrinology , medicine , hypophysectomy , glutathione , collagenase , triiodothyronine , biology , hepatocyte , glutathione s transferase , hormone , enzyme , chemistry , biochemistry , in vitro
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 (T 3 ) on the distribution of GST was studied in rats. Hypophysectomy increased total GST activity both in the periportal and perivenous liver region. Subsequent T 3 treatment counteracted this effect in the perivenous zone. However, analysis for either μ class M1/M2‐specific (1,2‐dichloro‐4‐nitrobenzene) or α class A1/A2‐specific (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 GST classes. In contrast, T 3 was found to significantly counteract the increase of α class GST activity caused by hypophysectomy in the periportal zone. To establish whether this effect was T 3 ‐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 T 3 suppressed the A1/A2‐specific GST activity and α class proteins predominantly in periportal cells. The data demonstrate that T 3 is an important factor responsible for the low expression of α GST in the periportal region. T 3 may be involved in the periportal downregulation of other phase I and II enzymes as well.