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 phos-phoenolypyruvate and 3-phosphoglycerate and elevated ratios of [ATP]/[ADP][P] and [NAD+/[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][P]and [NADP+]/[N DPH], 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 lev-els of phosphoenolypyruvate, 2-phosphoglycerate and ketone bodies were reversed. However, the calculated free cytoplasmic [A TP]/[ADP][P ratio and the calculated cytochrome c3+/cyto-chrome C2+ ratio did not return to control values. This suggests that those actions of thyroid hormone which are mediated by potentia-tion 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 con-sumption and A TP generation