Glinoer D, McGuire R A, Gershengorn M C, Robbins J, Berman M
Endocrinology. 1977 Jan;100(1):9-17. doi: 10.1210/endo-100-1-9.
To investigate the effects of estrogen on thyroxine-binding globulin (TBG) metabolism, 4 female Rhesus monkeys were studied before and 3-4 weeks 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 mug/ml, was elevated by 24 h after E2 implantation, and reached a steady level of 46.8 +/- 5.0 mug/ml by 7-10 days. For the turnover studies, highly purified [125I]iodo-TBG was injected iv and serum [125I]PBI and urinary 125I 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 early E2 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 first 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 weeks 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 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 we have recently found in monkey hepatocytes studied in vitro after isolation from E2-treated animals. It appears that stimulation of hepatic synthesis of TBG accounts for the elevated serum levels of TBG observed after estrogen.
为研究雌激素对甲状腺素结合球蛋白（TBG）代谢的影响，对4只雌性恒河猴在植入含β-雌二醇（E2）的胶囊之前及之后3 - 4周进行了研究。此外，对其中2只动物在开始使用E2后的前7天也进行了研究。血清E2从20±7 pg/ml增至212±41 pg/ml，升高了10倍。血清TBG最初为20.2±6 μg/ml，在植入E2后24小时即升高，至7 - 10天时达到稳定水平46.8±5.0 μg/ml。对于周转率研究，静脉注射高纯度的[125I]碘代TBG，每日测定血清[125I]PBI及尿125I排泄量。通过使用房室模型评估TBG动力学。虽然两房室模型足以拟合对照期和E2后期的数据，但为了解释在E2早期观察到的变化，开发了一个三房室模型。对照期TBG的最终衰减率（k）为0.26±0.01/天，E2后略低（0.23±0.01/天）。在E2早期研究的2只猴子中，E2的主要作用是刺激TBG的产生率。在模型中通过E2后第一天最后四分之一时间内的逐步增加来模拟这种情况。在模型定义的各房室中TBG也有突然的重新分布。E2使用3 - 4周后TBG的总分布或血清等效体积增加了1.4倍，从338±37 ml增至458±22 ml，代谢清除率增加了1.3倍，从90±10 ml/天增至113±12 ml/天。最终TBG产生率的增加（2.9倍）仅略高于E2早期计算的速率，且与我们最近在从经E2处理的动物分离后体外研究的猴肝细胞中发现的增加相似。看来雌激素后观察到的血清TBG水平升高是由于肝脏合成TBG受到刺激所致。
