Effect of thyroid hormone administration on the depletion of circulating glutathione in the isolated perfused rat liver and its relationship to basolateral γ‐glutamyltransferase activity

Abstract

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 (T3)/kg. T3 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-serineborate (4 mM) to the perfusate abolished the increase in the hepatic removal of GSH elicited by T3, 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 T3-induced oxidative stress.

Hepatic glutamate transport and glutamine synthesis capacities are decreased in finished vs. growing beef steers, concomitant with increased GTRAP3-18 content

“…The enrichment of GGT activity in the cLPM (29-fold) and bLPM (16-fold) vesicles vs. bovine liver homogenates (Table 2 ) is consistent with the previous findings that GGT is highly enriched in canalicular membranes isolated from rat and human liver (Inoue et al 1983 ; Poupon and Evans 1979 ; Meier et al 1984 ) and the 4–19-fold enrichment of the canalicular markers in bLPM isolated from rat liver (Meier et al 1984 ). The demonstration of GGT activity in both cLPM and bLPM vesicles isolated from bovine liver is consistent with histochemical studies, showing that GGT is distributed in both canalicular and basolateral membranes of rat and pig liver (Lanca and Israel 1991 ; Videla and Fernández 1995 ; Carrion et al 1993 ).…”

Long-living growth hormone receptor knockout mice: Potential mechanisms of altered stress resistance

“…The expression of this protein is regulated by hormones, amino acid availability, and GSH feedback inhibition (Griffith, 1999; Lu et al, 1990). Insulin and thyroid hormone have been shown to induce and suppress liver GCLC activity, respectively (Videla and Fernandez, 1995). Plasma insulin and thyroid hormone concentrations are low in GHR KO mice and possibly contribute to the differences in GCLC observed in this study.…”

Energy metabolism, thyroid calorigenesis, and oxidative stress: functional and cytotoxic consequences

“…Conversion of the hyperthyroid state to the euthyroid condition occurs in conjunction with the recovery of hepatic GSH levels, coinciding with a substantial elevation in sinusoidal γ-glutamyltransferase ectoactivity 63 and in removal of circulating GSH by the liver. 64 This was proposed to represent an adaptive response to recover hepatic GSH levels, after depletion by the initial T 3 -induced oxidative stress, by supplying the precursors for intracellular synthesis of the tripeptide. 63,64 Interestingly, hyperthyroidism substantially enhances the hepatic content of ubiquinone (coenzyme-Q), 65,66 the well known electron and proton carrier in the mitochondrial respiratory chain with antioxidant activity.…”

“…64 This was proposed to represent an adaptive response to recover hepatic GSH levels, after depletion by the initial T 3 -induced oxidative stress, by supplying the precursors for intracellular synthesis of the tripeptide. 63,64 Interestingly, hyperthyroidism substantially enhances the hepatic content of ubiquinone (coenzyme-Q), 65,66 the well known electron and proton carrier in the mitochondrial respiratory chain with antioxidant activity. 67 However, this effect occurs after the increment in BMR and, therefore, in free radical production, 66 suggesting an adaptive response of the liver to oxidative stress involving a derangement of other antioxidant mechanisms.…”