Inhibition of the effects of thyroid hormone on rat liver by 5,5'-diphenylthiohydantoin.
Metabolites were measured in freeze-clamped livers from rats that had been maintained for 3 weeks on a stock diet supplemented with 0.1% 5,5'-diphenylthiohydantoin (DPTH). Compared with control animals, DPTH-treated animals had lower levels of phosphoenolypyruvate and 3-phosphoglycerate and elevated ratios of [ATP]/[ADP][Pi] and [NADP+]/[NADPH], suggesting mild hypothyroidism. Conversely, the administration of thyroxine (T4) for 5 days to animals fed the control diet resulted in elevated levels of phosphoenolpyruvate, 3-phosphoglycerate, and ketone bodies and lowered ratios of [ATP]/[ADP][Pi] and [NADP+]/[NADPH], consistent with the known effects of thyroid hormones on liver tissues. In animals simultaneously treated with DPTH and T4, the effects of thyroxine on the [NADP+]/[NADPH] ratio and the levels of phosphoenolypyruvate, 2-phosphoglycerate and ketone bodies were reversed. However, the calculated free cytoplasmic [ATP]/[ADP][Pi] ratio and the calculated cytochrome c3+/cytochrome c2+ ratio did not return to control values. This suggests that those actions of thyroid hormone which are mediated by potentiation of adrenergic effects are reversed by DPTH. These actions include a decrease in peripheral lipolysis, a reduction of the free cytoplasmic [NADP+]/[NADPH] ratio, and an apparent inhibition of the pyruvate kinase reaction, but DPTH apparently does not reverse the effects of thyroid hormone on mitochondrial O2 consumption and ATP generation.
D000227:Adenine Nucleotides / Q000378:metabolism; D000818:Animals; D013956:Antithyroid Agents; D002952:Citric Acid Cycle / Q000187:drug effects; D006019:Glycolysis / Q000187:drug effects; D007657:Ketone Bodies / Q000378:metabolism; D008099:Liver / Q000187:drug effects*; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism; D010084:Oxidation-Reduction; D010672:Phenytoin / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013963:Thyroid Hormones / Q000494:pharmacology*; D013974:Thyroxine / Q000494:pharmacology
D000227:Adenine Nucleotides; D013956:Antithyroid Agents; D007657:Ketone Bodies; D013963:Thyroid Hormones; D010672:Phenytoin; D013974:Thyroxine