The Mechanism of Damping of the Serum Thyroxine and Triiodothyronine Levels Caused by Increasing Thyrotropin Dosage in Mice

The time course of the effect of bovine TSH (bTSH) on serum concentrations of thyroxine (T4) and triiodothyronine (T3) was measured in the normal mouse. The basal, unstimulated levelswere 3.2 ° 1.1 µ.g/100 ml T4 and 104 ° 25 ng/100 ml T3 (mean ° SD). With doses of bTSH from 0.5 to 100 mU the peak levelsof the thyroid hormones were only 2.6 and 1.8 times the basal level for T4 and T3, respectively. With increasing doses of bTSH there was a proportional prolongation of the increased serum levels of thyroid hormones, i.e., about 2 h for 0.5 mU to 12 h for100 mU TSH. The integrated response with time was linearly related to the log dose. This would suggest a control mechanism which prevents excessive concentration of thyroid hormones in the serum. This patternof response to TSH differs somewhat from that obtained by following radioiodine release in the McKenzie type bioassay. To avoid the problems of changing blood concentrations of thyroid hormones and TSH, the releaseof T4 and T3 from the mouse thyroid was measured in vitro. The secretion increased with bTSH concentrations in the range of 0.02−0.8 mU/ml for T4 and 0.02−0.1 mU/ml for T3. The maximal response was 8.8 ° 0.5 ng T4−3 h/thyroid and 3.6 ° 0.3 ng T3/3 h/thyroid as against the basal secretion of 2.4 ° 0.2 ng T4 and 0.8 °0.1 ngT3 (mean ° SEM). Further increase in bTSH concentration was associated with a decreased rate of thyroid hormone release. Thyroidal cAMP accumulation was enhanced withincreasing bTSH concentration, even when there was a decrease in secretion. The dichotomy in the dose-response pattern betweenthe two parameters indicated that the effect of high TSH concentrations on the release was inducedat a step beyond cAMP accumulation. This was corroborated by the similar pattern of release induced by increasing concentrations of DBcAMP. These findings indicate the existence of an intrathyroidal autoregulatory mechanism which prevents excessive increase of thyroid hormone levels in, the blood.