Endocrinology, Vol 100, 1621-1627, Copyright © 1977 by Endocrine Society

ARTICLES

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

WH Dillmann, HL Schwartz, E Silva, MI Surks and JH Oppenheimer

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.

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				J. Oppenheimer Thyroid hormone action at the cellular level Science, March 9, 1979; 203(4384): 971 - 979. [Abstract] [PDF]