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

Abstract

.alpha.-Amanitin inhibited triiodothyronine (T3)-induced increases in mitochondrial .alpha.-glycerophosphate dehydrogenase (.alpha.-GPD) and cytoplasmic malic enzyme activity in the livers of male Sprague-Dawley rats. A 3-fold increase in .alpha.-GPD observed 24 h after the i.v. injection of 3 .mu.g T3/100 g BW [body weight] was completely inhibited by administration of .alpha.-amanitin at 0 and 8 h. Similarly, .alpha.-amanitin blocked a 2- to 4-fold increase in malic enzyme 24 h following i.v. injection of 3 mg T3/100 g BW into euthyroid rats. After the initial inhibition of enzyme induction by .alpha.-amanitin was dissipated; a delayed but striking increase in enzyme activity occurred. In hypothyroid animals, .alpha.-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 in enzyme response is most easily explained by the formation of a long-lived intermediate during the exposure of the nuclear sites to T3.