Effect of Dose of Thyroid Hormone on the Sensitivity of the McKenzie Bioassay*

Abstract

Florsheirn reported that large doses of thyroid hormone, when employed for suppression of intrinsic TSH in McKenzie assay mice, reduced the response of the animal to TSH or LATS. Accelerated radioiodine clearance was proposed for the mechanism of this reduction in the response. We sought to determine whether thyroidal responsiveness per se is influenced by the dose of thyroid hormone, adopting radioiodine release and intracellular colloid droplet formation as parameters of thyroid response. A daily dose of T3, 0.5, 10, 25 μg, or T4, 0.5 or 25 μg was injected SC into mice for three days after 125I injection. On the day after the last thyroid hormone injection, they received 0.075 mU TSH or LATS-IgG. Blood radioactivity and response index were obtained on the specimens taken before, 2½ or 8 hr after the injection. Colloid droplet counts were obtained on the thyroid gland removed at ½ hr after TSH or 2 hr after LATS-IgG. The dose of TSH or LATS, which caused sizable and significant extent of radioiodine release in mice pretreated with 0.5 μg T3, failed to do so in mice with 25 μg T3. The colloid droplet response to TSH or LATS was markedly reduced in mice pretreated with 25 μg T3 or T4 when compared to that in mice given 0.5 μg T3. This effect of a large dose of thyroid hormone was only partially reproduced by the equivalent dose of iodide. The reduction in the colloid droplet response was also observed in thyroid glands of mice pretreated with large doses of T3in vivo and incubated with TSH or LATS-IgG in vitro. Our study thus demonstrates a reduction of bioassay response in McKenzie assay mice pretreated with a large dose of thyroid hormone being due to the decreased thyroidal responsiveness to stimulators. (Endocrinology95: 922, 1974)