Effect of Thiouracil-type Drugs on the α-Glycerophosphate Dehydrogenase Response to Thyroxine Analogs

The response of mitochondrial α-glycerophosphate dehydrogenase (GPD) activity to the injection of T4, T3, Tetrac, Triac, Tetraprop, Triprop and isopropyl-T2 was determined in liver, kidney and heart of weanling male rats maintained on a purified diet containing 2-thiouracil (TU). Similar studies were done with T4 and T3 in the presence of 6-propylthiouracil (PTU) and 2-mercapto-l-methylimidazole (MMI). TU inhibited the GPD response to T4 in all tissues, but did not decrease the response to T3 or the other analogs. PTU also inhibited T4 but not T3, while MMI had no effect on either. TU actually enhanced the GPD response to Tetraprop, Triprop and isopropyl-T2, and in some cases the liver GPD response to Triac and T3. The effect of TU on the GPD responses to T4, T3, Tetrac and Triac correlated well with the metabolic rate responses to these compounds. The extrathyroidal inhibition of T4 by thiouracils precludes the use of these drugs in antigoitrogenic assay procedures or in the estimation of endogenous T4 output. Such results with MMI appear to be valid for T4 and T3 since this drug also blocks synthesis in the gland but does not inhibit the peripheral effect of either compound. The peripheral inhibition of T4 by TU does not appear to be due to the incorporation of TU into the RNA of rat tissues, since the activities of all the analogs were not inhibited. (Endocrinology78: 1189, 1966)