The Effect of Graded Doses of Thyroxine on Plasma Thyrotropin Concentration in Rats Made Hypothyroid by Thyroidectomy or Propylthiouracil*

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Abstract
Adult male rats were made chronically hypothyroid by surgical thyroparathyroidectomy or by feeding propylthiouracil. In one set of experiments, each rat was injected ip daily with doses of T4 ranging from 0.01–3.0 μg/100 g BW, which were progressively increased every 3 days. Compared to the saline-treated controls, there was no statistically significant depression of plasma TSH until doses of 0.3 μg T4/100 g BW daily had been exceeded; there was no significant rise in plasma TSH with any dose of T4. No difference was detected in the quantitative suppression of plasma TSH concentration in the thyroidectomized or propylthiouracil-treated rats, even though a given dose of T4 caused a greater rise in plasma T4 concentration in the latter. In a separate experiment, chronically thyroidectomized rats injected for 3 days with saline or with 0.01, 0.1, or 1 μg T4 for 3 days were given 100 ng TRH/100 g BW iv. There was no effect on the rise in plasma TSH produced by TRH in any group, except in the group receiving the largest dose of T4 in which there was a significant depression. Our data indicate that there is no positive effect of small doses of T4 which will increase plasma TSH in chronically hypothyroid rats. They further indicate that the thyrostat of hypothyroid rats is insensitive to low doses of T4 and that there is a narrow range between the quantity of T4 required to induce minimal detectable suppression and that required to induce full suppression of TSH secretion to a normal or subnormal rate. (Endocrinology106: 818, 1980)