The role of 3,5,3'-triiodothyronine in the physiological action of thyroxine in the premetamorphic tadpole

In premetamorphic tadpoles precocious metamorphosis can be induced by immersion in water containing either T4 or T3. T3 5-deiodinase (5D) activity is present in most tissues, and T4 5'-deiodinase (5'D) activity is present in gut and skin; both systems can be inhibited by iopanoic acid (IOP). If conversion of T4 to T3 is important for the normal physiological action of T4 in these tadpoles, it follows that IOP should decrease the effects of T4 and increase those of T3 on metamorphic events. To test this, tadpoles were immersed in water containing either T4 or T3 (20 nM) with or without 1.75 microM IOP. Two indices of metamorphosis, increased leg length and hepatic carbamyl phosphate synthetase activity, were studied. In vehicle- or IOP-treated animals, change in leg length and carbamyl phosphate synthetase activity were minimal. Both indices were increased after exposure to T3 for 10 days or to T4 for 21 days. Moreover, the effects of T3 were significantly enhanced while those of T4 were inhibited when IOP was also present. Both 5'D and 5D activities determined in vitro were inhibited (95% and 60%, respectively) in IOP-treated tadpoles, and this was associated with an increase in the plasma concentration of hormone. In separate experiments, vehicle- and IOP-treated tadpoles received [125I]T4 or [125I]T3 ip. Plasma, liver, gut, and skin were examined 12-24 h later for 125I-labeled products. After [125I]T4 treatment [125I]T3 was found in skin and gut, but not in plasma or liver. After [125I]T3 treatment [125I]3,3'-diiodothyronine was identified in all extracts studied. In vivo generation of these products was reduced by 50% in IOP-treated tadpoles. These findings indicate that generation of T3 from T4 can take place in vivo in the premetamorphic tadpole and strongly support the hypothesis that this process plays an important role in the physiological action of T4 in this species.