Hepatic iodothyronine 5-deiodinase activity in Rana catesbeiana tadpoles at different stages of the life cycle

Abstract

Conversion of T4 to T3 cannot be demonstrated in vivo in Rana catesbeiana tadpoles until just before metamorphic climax, suggesting that 5'-deiodinase (5'D) activity is not present until this time. In the present study the role of 5-deiodinase (5 D) systems in the metabolism of T4 and T3 in the developing tadpole was examined. 5 D activity capable of converting T3 to 3,3'-diiodothyronine, and T4 to rT3 was present in hepatic microsomes from pre- and prometamorphic tadpoles, but it declined to undetectable levels during metamorphic climax. The preferred substrate was T3. The Vmax for T3 in premetamorphic tadpoles was 30.4 +/- (SE) 6.37 fmol/min X mg microsomal protein, and the Michaelis-Menten constant (Km) was 3.6 +/- 0.72 nM, respectively. The characteristics of the system are similar to those of the type III iodothyronine deiodinase present in mammals. The system has its counterpart in vivo; administration of T3 or T4 to tadpoles resulted in the generation of detectable amounts of the corresponding 5-deiodinated product. rT3 was also shown to be a naturally occurring iodothyronine in this species. Although generation of T3 from T4 was readily demonstrable in vivo in tadpoles that had entered metamorphic climax, hepatic 5'D activity determined in vitro was found to be extremely low at all stages of development. On the basis of these findings, the following alternative explanation for the failure to observe T4 to T3 conversion before climax is offered. In pre- and prometamorphic tadpoles, any T3 produced from T4 is rapidly converted to 3,3'-diiodothyronine by the 5 D system and thus accumulation is prevented. Once climax has begun, 5 D activity declines and thus the T3 generated is able to accumulate. Whether the increased T3 accumulation is also facilitated by an increase in T3 production due to increased 5'D activity remains to be determined.