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][P i ] 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][P i ] 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 02 consumption and A TP generation.