Tyrosine Hydroxylase and the Conversion of L-Thyroxine into 3′,3,5-Triiodo-L-Thyronine in the Rat*

Abstract

We have studied the effects of α-methyl-p-tyrosine (α-MPT), an inhibitor of tyrosine hydroxylase, on the in vivo conversion of L-T₄ (T₄) to 3′,3,5-triiodo-L-thyronine (T₃), and on the biological effectiveness of T₄. Thyroidectomized rats were used and were injected daily with T₄ maintenance doses. Three different types of experiments were carried out. The first involved isotopic equilibration with ¹²⁵I-labeled T₄ and measurement of urinary ¹²⁵I excretion. The second series involved the injection of a single dose of [¹²⁵I]T₄, with the amounts of [¹²⁵I]T₃ in different tissues being studied 7 or 20 h later. The third series involved daily treatment for 13 days with T₄ and α-MPT, at the end of which the liver α-glycerophosphate dehydrogenase activity was measured as a parameter of the biological effects of the hormone. Though the experimental approaches used clearly disclosed the well known effects of 6-propyl-2-thiouracil, no clear-cut effects of α-MPT were observed. It is concluded that a-MPT neither inhibits the conversion of T₄ to T₃in vivo in rats nor affects the biological potency of a given dose of T₄, at least to an extent comparable to that observed when 6-propyl-2-thiouracil is used. Thus, present results do not support the hypothesis that tyrosine hydroxylase is involved in the extrathyroidal deiodination of T₄ to T₃.