The present study was undertaken to examine whether long acting thyroid stimulator (LATS) induces refractoriness of thyroid hormone synthesis and thyroid hormone secretion to the stimulator in vivo. Male DDY mice fed with a low iodine diet and given 5 \g=m\g/ml of triiodothyronine (T3) in drinking water ad libitum for 4 days were injected with 0.25 ml of LATS positive serum (1000%/0.25 ml in the McKenzie bioassay) ip every 24 h for 9 days. Groups of 5 mice were sacrificed before and 1, 3, 5, 7 and 9 days after the first injection of LATS for the determinations of serum thyroxine (T4) concentrations, the 1 h thyroid 131I uptake and thyroid weight. Control mice were injected with LATS negative pooled normal sera. Serum T4 concentrations elevated significantly 24 h after the 3rd injection of LATS and remained elevated until the end of the experiment. One hour thyroid 131I uptake elevated about 3-fold 24 h after the first injection of LATS. It further increased 24 h after the 3rd injection of LATS to 10-fold of the value for control animals and stayed elevated at this same level for the remainder of the study.These results indicate that stimulating effects of LATS on thyroid hormone synthesis assessed by thyroid 131I uptake and thyroid hormone secretion assessed by serum T4 concentrations were not diminished by the prior administration of the stimulator. These findings suggest that LATS does not induce refractoriness of either thyroid hormone synthesis or thyroid hormone secretion to the stimulator in mice in vivo.
Since 1976 when Shuman et al. (1976) demonstra¬ted that the exposure of thyroid slices to thyroid stimulating hormone (TSH) induces refractoriness of the cyclic AMP system to subsequent hormone stimulation in vitro, many studies have been done with regard to refractoriness to TSH in thyroid tissue. Field et al. (1977) demonstrated refractori¬ ness to TSH of thyroid protein kinase, glucose oxidation and phospholipid synthesis. Rapoport 8c Adams (1976) showed refractoriness to TSH of thyroid cAMP response in cultured thyroid cells. Furthermore, recently Field et al. (1979) reported refractoriness to TSH of iodine organification in vitro and thyroid hormone secretion in vivo. Thus, refractoriness to TSH is a well-known pheno¬ menon and is supposed to be physiologically im¬ portant in controlling thyroid function to stimula¬ tion with TSH.