Evidence for the rapid direct control both in vivo and in vitro of the efficiency of oxidative phosphorylation by 3,5,3′-tri-iodo-l-thyronine in rats

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Abstract
Examination of the distribution of L-triiodothyronine [T3] among rat liver tissue fractions after its i.v. injection into thyroidectomized rats focused attention on mitochondria at very short times after administration. By 15 min this fraction contained 18.5% of the tissue pool; however, the content had decreased sharply by 60 min and even further over the next 3 h. By contrast, the content in all other fractions was constant or increased over 4 h. About 60% of tissue hormone was bound to soluble protein. Mitochondria isolated from thyroidectomized rats showed P/O [mol of Pi esterified/g-atom of O consumed] ratios that were about 50% of those found in normal controls, with both succinate and pyruvate plus malate as substrates. There was no evidence of uncoupling; the respiratory-control ratio was about 6. Mitochondria isolated 15 min after injection of T3 into thyroidectomized rats showed P/O ratios and respiratory-control ratios that were indistinguishable from those obtained in mitochondria from euthyroid animals. The oxidation rate was, however, not restored. Incubation of homogenates of livers taken from thyroidectomized animals injected with L-T3 before isolation of the mitochondria restored the P/O ratio to normal; direct addition of hormone to isolated mitochondria had no effect. The role of extramitochondrial factors in rapid T3 action is discussed. Possible mechanisms by which T3 might rapidly alter phosphorylation efficiency are considered; control of adenine nucleotide translocase is unlikely to be involved. The amounts of adenine nucleotides in liver were measured both after thyroidectomy and 15 min after i.v. T3 thyronine administration to thyroidectomized animals. The concentrations found are consistent with a decreased phosphorylation efficiency in thyroidectomized animals. T3 injection resulted in very significant changes in the amounts of ATP, ADP and AMP, and in the [ATP]/[ADP] ratio, consonant with those expected from an increased efficiency of ADP phosphorylation. The changes seen in isolated mitochondria may indeed reflect a rapid response of liver in vivo to T3.