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

D. GLINOER, R. A. McGUIRE, A. DUBOIS, J. P. COGAN, J. ROBBINS and M. BERMAN

Clinical Endocrinology Branch, National Institute of Arthritis, Metabolism, and Digestive Diseases, Laboratory of Theoretical Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20014; and the Veterans Administration Hospital

Address requests for reprints to: Dr. Robbins, Building 10, Room 8N315, National Institutes of Health, Bethesda, Maryland 20014.

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.

Footnotes

^* This work was presented in part at the 59th Annual Meeting of The Endocrine Society, June 8-10, 1977, Chicago, IL.

Supported in part by a PHS International Research Fellowship (F05 TW-2165).

Department of Internal Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20014.

Division of Pathology, Bureau of Biologies, Food and Drug Administration, Bethesda, Maryland 20014.

Received February 27, 1978.