L-Thyroxine in Subcalorigenic Doses: Rapid Potentiation of Dinitrophenol-Induced Calorigenesis in Hypothyroid Rats

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Abstract
The calorigenic action of 2,4-dinitrophenol (DNP), measured as percentage of increase in BMR 30-45 min after ip injection of 10 [mu]g/g body wt, was less in about 40% of the hypothyroid rats in this study than it was in euthyroid ones. The remaining hypothyroid rats, with a similar BMR to those responding subnormally, had a normal percentage of calorigenic response to DNP; in these rats L-thyroxine (L-T4), 50-300 m[mu]g/g given over 3 days, raised the BMR and increased DNP-induced calorigenesis above normal. Those hypothyroid rats with low DNP-induced calorigenesis were more sensitive to L-T4: a single ip dose of 5.2 m[mu]g/g of L-T4, with no calorigenic action itself, restored 85% of their calorigenic response to DNP in 6 hr, but did not change the response of rats with normal DNP-induced calorigenesis. The restored calorigenic response to DNP lasted 1-2 weeks and could again be raised with L-T4. Since DNP is calorigenic by acting on mitochondrial oxidative phosphorylation in vivo, L-T4 acts here either to allow more DNP to reach the mitochondria or to increase their reactivity. The dose of L-T4 is to small to act by displacing DNP from common protein-binding sites. The efficacy and rapidity of the potentiation of DNP-induced calorigenesis in hypothyroid rats suggest that it reflects a primary action of L-T4.