IDENTIFICATION OF 3,3'-DIIODOTHYROACETIC ACID SULFATE - A MAJOR METABOLITE OF 3,3',5-TRIIODOTHYRONINE IN PROPYLTHIOURACIL-TREATED RATS

The sulfate conjugate 3, [3’-125I] diiodothyroacetic acid (3, 3’-TA2S) was discovered in plasma, and occasionally in bile, of 6-propyl-2-thiouracil-treated rats after administration of [125I]T3. The identification of this T3 metabolite was based on the following evidence: 1) the compound co-eluted in two different HPLC systems with synthetic 3, 3’-TA2S; 2) its chromatographic behavior on Sephadex LH-20 was characteristic for a conjugated iodothyronine derivative; and 3) the metabolite was hydrolyzed by arylsulfatase and the liberated product comigrated with synthetic 3, 3’-TA2 on HPLC. Marked accumulation of 3, 3’- TA2S was observed only in rats with impaired type I deidodinase activity but not in controls. Furthermore, plasma and biliary 3, 3’-TA2S levels varied with the experimental conditions such as anesthesia, i.e. both were increased in ketamine-anesthetized over pentobarbital-anesthetized animals. It was not possible to indicate the exact pathway through which 3, 3’-TA2S is generated from T3; neither is it known how much of T3 is acutally metabolized via 3, 3’-TA2S. However, the significant plasma 3, 3’-TA2S levels, even in unanesthetized animals, illustrate the physiological relevance of this T3 metabolite. © 1990 by The Endocrine Society.