Alpha-amanitin was shown to inhibit triiodothyronine (T3)-induced increases in mitochondrial alpha-glycerophosphate dehydrogenase (α-GPD) and cytoplasmic malic enzyme activity in the livers of male Sprague-Dawley rats. A 3-fold increase in a-GPD observed 24 h after the iv injection of 3 μg T3/100 g BW was completely inhibited by administration of alpha-amanitin at 0 and 8 h. Similarly, alpha-amanitin blocked a two-to four-fold increase in malic enzyme 24 h following iv injection of 3 mg T3/IOO g BW into euthyroid rats. After the initial inhibition of enzyme induction by alphaamanitin was dissipated, however, a delayed but striking increase in enzyme activity occurred. In hypothyroid animals, α-GPD activity rose after the initial 24 h inhibition and reached levels at 72 h equal to those observed in hypothyroid rats treated with T3 only. In euthyroid animals treated with T3 and alpha-amanitin, a delayed increase in malic enzyme activity was observed at 72 h and attained values at 96 h similar to those in euthyroid animals injected with T3 only. The delayed rise inenzyme response is most easily explained by the formation of a long-lived intermediate during the exposure of the nuclear sites to T3.
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