Autoregulation of 3, 3',5'-triiodothyronine production by rat liver microsomes

Abstract

Abstract.: Conversion of thyroxine (T 4) to 3,3′,5′-triiodothyronine (rT 3) was studied in rat liver microsomes. Addition of rT 3 at a physiological concentration to the incubation medium inhibited the deiodination of thyroxine to rT 3. With a concentration of rT 3 greater than 37.6 n M no net rT 3 production at pH 8.0 was observed. Further increases in rT 3 concentration resulted only in degradation of added rT 3 and no net synthesis of rT 3 from T 4 could be detected. The inhibitory effect of rT 3 upon its own production from T 4 was pH dependent, 5 fold lower amounts of hormone being required to inhibit completely rT 3 production at pH 7.4 than at pH 8.0. With the same experimental conditions no significant effect of rT 3 on the conversion of T 4 to 3,5,3′-triiodothyronine (T 3) could be observed at pH 8.0 with all concentrations of added iodothyronine. A linear production of 3,3′-T 2 from added rT 3 was determined over the whole range of rT 3 concentration, suggesting a lack of saturation of deiodinating enzyme. Binding of rT 3 by anti-rT 3 antibody added to the incubation mixture enhanced rT 3 production from T 4 by protecting rT 3 from being degraded and/or diminishing the inhibitory effect of this iodothyronine on its own production. It was concluded that rT 3 influenced its own production and that this effect may represent an important autoregulatory process in the iodothyronine metabolism.