EFFECT OF THYROID-HORMONE ADMINISTRATION ON THE DEPLETION OF CIRCULATING GLUTATHIONE IN THE ISOLATED-PERFUSED RAT-LIVER AND ITS RELATIONSHIP TO BASOLATERAL GAMMA-GLUTAMYL-TRANSFERASE ACTIVITY

The influence of thyroid hormone administration on liver glutathione (GSH) extraction in the isolated perfused liver was studied in fed rats for a period of 1-7 days following a single dose of 0.1 mg 3,5,3'-triiodothyronine (T-3)/kg. T-3 treatment led to an early and transient calorigenic response, as well as an enhancement in liver GSH removal, reaching a maximal effect at 2 days after hormone administration, which was normalized in the 3- to 7-day period studied. Addition of the gamma-glutamyltransferase (gamma-GT) inhibitor DL-serine-borate (4 mM) to the perfusate abolished the increase in the hepatic removal of GSH elicited by T-3, and enhanced the sinusoidal concentration of GSH, studied at 2 days after hormone administration. These data support the role of hepatic basolateral gamma-GT ectoactivity in the depletion of portally added and liver-derived GSH as an adaptive response to recover GSH levels after reduction by T-3-induced oxidative stress.