Effects of Estrogen on Thyroxine-binding Globulin Metabolism in Rhesus Monkeys

Abstract

To investigate the effects of estrogen on thyroxine-binding globulin (TBG) metabolism, 4 female rhesus monkeys were studied before and 3-4 wk after implantation of .beta.-estradiol (E2)-containing capsules. In addition, 2 of the animals were also studied for the first 7 days after the start of E2. Serum E2 increased 10-fold from 20 .+-. 7 to 212 .+-. 41 pg/ml. Serum TBG, initially 20.2 .+-. 6 .mu.g/ml, was elevated by 24 h after E2 implantation, and reached a steady level of 46.8 .+-. 5.0 .mu.g/ml by 7-10 days. For the turnover studies, highly purified [125I]iodo-TBG was injected i.v., and serum [125I]PBI [protein bound I] and urinary 125 excretion were measured daily. TBG kinetics were evaluated by use of a compartmental model. Although a 2-compartment model was sufficient to fit the control and late E2 data, a 3-compartment model was developed in order to account for the modifications observed during the early E2 period. The final decay rate (k) of TBG was 0.26 .+-. 0.01/day during the control period and was slightly lower after E2 (0.23 .+-. 0.01/day). In the 2 monkeys studied during the E2 early period, the major effect of E2 was a stimulation of the TBG production rate. This was simulated in the model by a stepwise increase occurring in the last quarter of the 1st day after E2. There was also an abrupt redistribution of TBG in the compartments defined by the model. The total distribution or serum equivalent volume of TBG after 3-4 wk of E2 increased 1.4-fold, from 338 .+-. 37 ml to 458 .+-. 22 ml, and the metabolic clearance rate increased 1.3-fold, from 90 .+-. 10 ml/d [day] to 113 .+-. 12 ml/d. The increase in the final TBG production rate (2.9-fold) was only slightly greater than the rate calculated for the early E2 period and was similar to the increase recently found in monkey hepatocytes studied in vitro after isolation from E2-treated animals. Stimulation of hepatic synthesis of TBG apparently accounts for the elevated serum levels of TBG observed after estrogen.