Incomplete Suppression of Thyrotropin Secretion after Single Injection of Large L-Triiodothyronine Doses into Hypothyroid Rats

In order to examine the mechanism underlying incomplete suppression of TSH secretion by thyroid hormones, we measured serum TSH and T3 levels (radioimmunoassay) in 3,5,3'-triiodothyromine (T3)-injected groups of euthyroid and hypothyroid rats. In 2 experiments, euthyroid rats received a single injection of 10 mug T3 and 25 mug T3/100 g body weight (BW). After T3 injection, the TSH levels fell rapidly to the undetectable range of the assay (1-5 ng/ml) within 3 h. TSH concentration returned to control levels following reduction of plasma T3 to pre-injection values as a result of hormone metabolism. Hypothyroid rats were used in the remaining experiments. They were injected with T3, 25 mug/100 g BW in 2 studies and 1000 mug/100 g BW in one. TSH levels in vehicle-injected groups were relatively constant for 9 days. In T3-injected groups, TSH decreased rapidly to about 10% of pre-injection concentrations within 5 hours. In the 3 studies, TSH remained at 100 ng/ml, 40 ng/ml and 30 ng/ml for 3-6 days despite markedly elevated T3 values. TSH then increased toward pre-injection values when T3 concentrations decreased to the euthyroid range. In an additional study, the daily injection of T3, 1 mug/100 g BW, resulted in a further decrease in plasma TSH to undetectable values only after 15-25 days. These studies show 2 components of TSH suppression in hypothyroid rats. Ninety per cent suppression occurs rapidly (hours) after a large dose of T3 Suppression of the residual TSH to the undetectable assay range occurs slowly, requiring prolonged (15-25 days) T3 administration. Further studies showed that TSH isolated from plasma of hypothyroid rats after T3 injection had an apparent molecular weight of 29,000 Daltons and exhibited an immunoassay curve parallel to rat TSH RP-1. Persistent secretion of TSH in the face of very high plasma T3 concentrations may reflect partial autonomy of thyrotrophs in TSH secretion or a nonspecific leak of TSH which is related in amount to the number of thyrotrophs present and/or their secretory activity in different thyroid states.