Potentiation of thyroxine 5-deiodination by aminotriazole.
Aminotriazole, a goitrogen, in addition to its known inhibitory effects on the thyroid, demonstrated a unique effect on peripheral deiodination of thyroxine (T4). In contrast to the well-known peripheral effects of goitrogens such as propylthiouracil in inhibiting 5'-deiodinase activity, i.e., to effect a decrease in T4 to triiodothyronine (T3) conversion, aminotriazole had no effect on the 5'-deiodinative pathway. Rather, this goitrogen appeared to stimulate the alternative pathway, viz. T4 5-deiodination, resulting in an increased reverse triiodothyronine (rT3) serum concentration. This was shown in comparisons of serum T4, T3 and rT3 concentrations and serum T3/T4 and rT3/T4 ratios between rats treated with aminotriazole and T4, and rats treated with T4 alone. The finding that aminotriazole may specifically enhance T4 5-deiodination, independently of T4 5'-deiodination, is novel, as this has not been observed in the case of other goitrogens. It is of interest that this goitrogen is devoid of sulphur, which is a prominent constituent of thiourylene compounds which have been noted to affect 5'-deiodination. The potentiating effect of aminotriazole on 5-deiodination of T4 was not attributable to dietary factors.
D000640:Amitrole / Q000494:pharmacology*; D000818:Animals; D006042:Goiter / Q000139:chemically induced; D007455:Iodine / Q000378:metabolism; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013974:Thyroxine / Q000097:blood / Q000378:metabolism*; D014230:Triazoles / Q000494:pharmacology*; D014284:Triiodothyronine / Q000097:blood; D014285:Triiodothyronine, Reverse / Q000097:blood
D014230:Triazoles; D014284:Triiodothyronine; D014285:Triiodothyronine, Reverse; D007455:Iodine; D013974:Thyroxine; D000640:Amitrole