title: 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 was shown to inhibit 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 iv injection of 3 microngT3/100 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 T3/100 g BW into euthyroid rats. After the initial inhibition of enzyme induction by alpha-amanitin was dissipated, however, 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.
mesh_terms: D000546:Amanitins / Q000494:pharmacology*; D000818:Animals; D004790:Enzyme Induction / Q000187:drug effects; D005993:Glycerolphosphate Dehydrogenase / Q000096:biosynthesis; D007037:Hypothyroidism / Q000201:enzymology; D008099:Liver / Q000201:enzymology*; D008135:Long-Acting Thyroid Stimulator / Q000502:physiology; D008291:Malate Dehydrogenase / Q000096:biosynthesis; D008297:Male; D051381:Rats; D013997:Time Factors; D014284:Triiodothyronine / Q000494:pharmacology*
chemical_list: D000546:Amanitins; D014284:Triiodothyronine; D008135:Long-Acting Thyroid Stimulator; D005993:Glycerolphosphate Dehydrogenase; D008291:Malate Dehydrogenase