Alpha-amanitin administration results in a temporary inhibition of hepatic enzyme induction by triiodothyronine: Further evidence favoring a long-lived mediator of thyroid hormone action

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.