Thyroxine-Binding Globulin Metabolism in Rhesus Monkeys: Effects of Hyper- and Hypothyroidism*

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Abstract
Metabolism of T4-binding globulin (TBG) was studied in rhesus monkeys after iv injection of trace amounts of 125I-labeled TBG. The animals were investigated during a control period, during experimentally induced hyperthyroidism (T3 toxicosis), and during hypothyroidism (6 weeks after thyroidectomy). Kinetic parameters were calculated from serum TBG levels (measured by RIA), serum [125I]PBI (shown to represent circulating radioactive TBG), and daily urinary excretion of radioiodide. A compartmental model was used to analyze the serum and urine data during each study period. During the control period, TBG was distributed in three compartments [serum equivalent volume or total distribution volume (SEV)] amounting together to 323 ± 23 ml (mean ± SEM)/3 kg BW or 11 ± 1% of the BW. The final decay rate (k) of TBG was 0.28 ± 0.01 day-1, the metabolic clearance rate (MCR) was 92 ± 10 ml/day, and the production rate (PR) was 2.23 ± 0.14 mg/day. During hyperthyroidism, several changes were observed. After 1 week of T3, there was a 33% decrease in serum TBG and no change in k. After 5 weeks of T3, circulating TBG had returned to normal, k was increased by 30%, MCR decreased by 12%, SEV by 33%, and PR by 13%. During hypothyroidism, opposite changes were observed in serum TBG (21% increase), k (51% decrease), and SEV (17% increase), but not in MCR (43% decrease) or PR (27% decrease). In summary, a comparison of hypothyroid, euthyroid, and hyperthyroid states showed a progressive decrease in the distribution volumes and in the fractional disappearance of TBG but a biphasic effect on the production rate. Whereas physiological concentrations of thyroid hormones increased TBG production, excess T3 decreased production. The respective roles of T3 and T4 in these effects requires further study.

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