Isopropyldiiodothyronine and α-methylthyroxine: Comparison of their in vitro and in vivo effects with those of thyroid hormones

Abstract

The in vivo and d in vitro effects of the two thyroid hormone analogs 3,5-diiodo-3′-isopropyl- L-thyronine (IPT 2) and of α-methyl- DL-thyroxine (MT 4) have been compared to those of the thyroid hormones 3,5,3′-triiodo- L-thyronine (T 3) and thyroxine (T 4). Against purified glutamate, isocitrate and alcohol dehydrogenases IPT 2 and MT 4 exert inhibitory effects which are quite similar to those exerted by T 3 and T 4. The effects of the analogs on isolated mitochondria follow closely those of the hormones i.e. they uncouple phosphorylations and inhibit electron transfer along the respiratory chain. When thyroidectomized animals are treated with analogs (5 nmoles/100 g/day for 15 days) their effects on two accepted parameters of thyromimetic activity, metabolic rate (BMR) and α-glycerophosphate (GPD) induction, are quite different. After IPT 2-treatment, the rise in MR and GPD indicates a hyperthyroid state, whereas MT 4-treatment results in very incomplete compensation of th hypothyroid state. However, treatment of the thyroidectomized animal with IPT 2 or MT 4 has the same effect on hepatic mitochondrial glutamate dehydrogenase as treatment with T 4. A relation between thyroid state and adrenal tyrosine hydroxylase (TH) activity has been established; TH activity which decreases in the thyroidectomized animal, is brought back to normal by administration of T 4 and above normal by that of IPT 2.