Evidence that the 5'-monodeiodinases for thyroxine and 3,3',5'-triiodothyronine in the rat pituitary are separate enzymes

Studies were directed at the question of whether the enzyme that mediates the 5'- or outer ring monodeiodination of T4 is the same as that which mediates the 5'-monodeiodination of rT3. Advantage was taken of previous observations which indicated that T3, when administered to the hypothyroid rat, acutely inhibits the 5'-monodeiodination of T4 to yield T3 in hemipituitaries in vitro. In the present experiments, these effects of T3 on the generation of T3 from T4 were confirmed in both hemipituitaries and homogenates, indicating that they were not due to an effect of T3 on the cellular penetration of the [125I]T4 used as substrate. In contrast, in separate experiments with both hemipituitaries and homogenates, T3 had no effect on the metabolism of [125I]rT3, including its 5'-monodeiodination to yield 3,3'-diiodothyronine. In other experiments, the divergent effects of T3 on the metabolism of T4 and rT3 were also observed when the two substrates were studied in paired hemipituitaries and paired aliquots of the same pituitary homogenate. Failure of T3 to inhibit the 5'-monodeiodination of rT3 in pituitary homogenates could not be explained by the presence of marked enzyme excess, since T3 was also without effect when homogenates were incubated with rT3 at a concentration of 1 microgram/ml. In additional experiments, propylthiouracil (PTU) in vitro (1 mM) was found to have no effects on either the rapid metabolism of [125I]T4 seen in the pituitaries of hypothyroid rats or the less rapid metabolism of [125I]T4 seen in pituitaries of hypothyroid rats given T3. In contrast, though PTU failed to alter the metabolism of [125I]rT3 in pituitaries of hypothyroid rats, it greatly inhibited the metabolism of [125I]rT3 in the pituitaries of hypothyroid rats given T3. These results are consistent with those in previous reports which indicate that the pituitary contains two enzymes that mediate the deiodination of T4 and rT3. One is a PTU-insensitive enzyme that mediates the 5'-monodeiodination of T4; its activity is increased in hypothyroidism and is decreased by T3 replacement. The other is a PTU-sensitive enzyme that mediates much of the 5'-monodeiodination of rT3 in the pituitary of the T3-replaced rat, as in the euthyroid rat, but whose activity is largely supplanted by that of the PTU-insensitive enzyme in hypothyroidism.