THYROID FUNCTION AND TRIIODOTHYRONINE AND THYROXINE KINETICS IN RABBITS IMMUNIZED WITH THYROID HORMONES

Abstract

ABSTRACT Neck-uptake studies, thyroid scintiscans and triiodothyronine (T3)- and thyroxine (T4)-kinetic studies were performed in normal rabbits and in animals producing antibodies against thyroid hormones. In immunized animals the radioiodide uptake and turnover were increased 3-fold and 6–17-fold, respectively. The thyroid glands were found to be enlarged scintigraphically and showed a denser tracer distribution pattern. T3 and T4 kinetic data were obtained from 5 rabbits immunized with T3 (ABT3), 4 immunized with T4 (ABT4) and from 5 controls. In T3 immunized animals total T3 in the serum rose from 86 to 59 000 ng/100 ml, in T4 immunized rabbits total T4 increased from 2.5 to 53.8 μg/100 ml. The fundamental principles of regulation were similar in both T3 and T4 immunized rabbits: There were enormous decreases in the total distribution spaces (TDS) as well as in the fractional turnover rates (k), resulting in markedly decreased metabolic clearance rates (MCR). The fall in T3-MCR was directly proportional to the T3 binding activity of the sera. However, striking differences between the respective alterations of T3 and T4 kinetic data were obtained in the immunized animals: T3-MCR fell about 70-fold in ABT3, whereas T4-MCR was diminished 15-fold in T4 immunized rabbits. In both groups of immunized animals T3-TDS decreased more than the T3 fractional turnover, whereas T4-TDS was less affected than k T4. The T3 production rates (PR) were increased 10-fold in ABT3 and 5-fold in ABT4, whereas the increases in T4-PR were of only moderate degree both in ABT3 and ABT4. Using presently available radiochemical methods the metabolic status of immunized rabbits could not be definitely assessed: "clinically" the animals were euthyroid. However, the dialyzable fraction in the serum of both T3 and T4 did not decrease proportionately to the enormous increase in total hormone concentration, so the free hormone concentrations were elevated over the normal. The results of the calculations of the cellular hormonal T3- and T4-clearance were more consistent with a euthyroid state: In ABT4 the cellular metabolism of both hormones was not different from the normal; in ABT3 a 1.7-fold increase in the cellular clearance of T3 was accompanied by a significant decrease of that in T4.