The identification of the acetic acid analogues of thyroxine and tri-iodothyronine in mammalian tissues.

The acetic acid analogues of thyroxine and tri-iodothyronine, namely tetraiodothyroacetic acid [4-(4'hydroxy-3':5'-di-iodophenoxy)3:5diiodophenylacetic acid] and tri-iodothyroacetic acid [4-(4'hydroxy-3'-iodophenoxy) 3:5 di iodophenylacetic acid] have been synthesized (Harington & PittRivers, 1952; Pitt-Rivers, 1953) and shown to possess considerable biological activity when assayed by the goitre-prevention test in rats (PittRivers, 1953). Pitt-Rivers suggested that tetraand tri-iodothyroacetic acids might arise during the peripheral metabolism of the thyroid hormones by oxidative deamination and decarboxylation of the alanine side chain of the parent amino acid. In support of this hypothesis Roche, Michel & Tata (1954) found that rats injected with large doses of tetraor tri-iodothyroacetic acid excrete the corresponding pyruvic acid analogue in their urine and bile. Traces of tri-iodothyroacetic acid have been detected in the kidney and muscle of rats given small doses tri-iodothyronine (Roche, Michel, Jouan & Wolf, 1956), and tetraiodothyroacetic acid was found in the serum of dogs injected with [L31I]thyroxine (Flock, Bollman, Grindlay & McKenzie, 1957). Tomita, Lardy, Larson & Albright (1957) detected tetraor tri-iodothyroacetic acid in ratkidney homogenates or cell-free extracts after incubation with thyroxine or tri-iodothyronine. Tata has obtained evidence that brain and muscle slices and homogenates can convert thyroxine and triiodothyronine into their respective acetic acid analogues (Tata, 1957; Tata, Rall & Rawson, 1957). It therefore appears that certain tissues can convert thyroxine and tri-iodothyronine into the corresponding acetic acid analogues, but it does not necessarily follow that this is a normal metabolic process. The experiments described below were carried out to determine whether the thyroacetic acids are formed from endogenous thyroid hormones after the administration of radioactive iodide.