Evaluation of the Peripheral Deiodination of L-Thyroxine as an Index of Its Thyrotrophin Suppressing Effectiveness

6-n-Propylthiouracil (PTU) injected ip in single low doses (10-500 μg/rat) induced an early response of the thyroid, consisting in an increased rate of discharge of 131I, a decrease in total 127I stores, and an alteration of the percentage distribution of 131I among iodinated compounds, in rats whose thyroids were labeled prior to injection of the drug and which were given CIO4- to block 131I recycling. This early response of the thyroid is likely to be due to an increase in TSH release, which confirms previous observations (19,20). It is shown here that the amount of exogenous L-thyroxine (L-T4) available to the animal determines the degree of response of the thyroid (and pituitary) to the injection of PTU. When the dose of exogenous L-T4 is high enough to ensure that about 0.7 to 1.0 μg of injected L-T4 is deiodinated (at least in the 3',5' position) per day, despite partial inhibition of deiodination caused by PTU treatment, there is no early thyroidal or hypophysial response to PTU. These findings, together with information reported previously (13), are consistent with the conclusion that the amount of L-T4 deiodinated peripherally is a better index of the effectiveness of this hormone as suppressor of TSH release than other metameters of thyroid hormone function. They further support the idea of the existence of some type of close correlation between the deiodination of L-T4 and its physiological activity, though a causal interrelationship cannot be postulated on the basis of the present data. No such correlation could be shown between deiodination of 3,3',5-triiodo-Lthyronine (L-T3) and its potency as suppressor of TSH release. (Endocrinology79: 248,196)