Reduced Clearance Rate of Thyroxine-Binding Globulin (TBG) with Increased Sialylation: A Mechanism for Estrogen-Induced Elevation of Serum TBG Concentration*

Abstract

Hyperestrogenemic states, including pregnancy, cause an increase in serum T4-binding globulin (TBG) concentrations and an increase in the proportion of TBG molecules with greater anodal mobility on isoelectric focusing, indicating greater sialic acid content. The possible causal relationship between the degree of sialylation and accumulation of TBG in serum was explored by measuring the in vivo half-lives (t1/2) of TBGs with different isoelectric points. TBG in unfractionated serum and its major peaks, isolated by chromatofocusing and defined by their isoelectric points on isoelectric focusing were each injected iv into rats. The resulting TBG concentrations, measured by specific RIA in serum samples obtained at intervals after injection, were used for the calculation of the t1/2. TBG in serum from a pregnant woman had a significantly longer t1/2 of 17.2 +/- 1.2 h (mean +/- SD) compared to those of 13.3 +/- 1.5 and 12.9 +/- 0.9 h for TBG in serum from a man and a nonpregnant woman, respectively. TBG peaks II, III, IV, and V, with increasing anodal mobility, had progressively longer t1/2 values of 11, 13, 15, and 33 h, respectively. However, TBG peaks of the same mobility on IEF isolated from serum of pregnant or nonpregnant subjects had similar t1/2 values. Neither the TBG concentration nor estrogen had a direct effect on the rate of TBG clearance. Indeed, the t1/2 of TBG from a subject with inherited TBG excess was not different from that of TBG from a nonpregnant woman or a man. Chronic treatment of rats with estradiol did not alter the rate of clearance of injected human TBG. Finally, the more heavily sialylated anodal bands of purified but unfractionated serum TBG, analyzed by Western blots, survived longer in the circulation of a rat. These results indicate that the rate of in vivo metabolism of TBG is dependent on its sialic acid content. The increased proportion of TBG molecules with higher sialic acid content thus contributes to the increase in the serum TBG concentration in hyperestrogenemic states.

Clinical and hormonal characteristics of central hypothyroidism at diagnosis and during follow-up in adult patients

“…The best characterized effect of estrogens is a dose-dependent increase of serum thyroxine-binding globulin (TBG), due to both a decrease in the clearance of heavily sialyated TBG secreted by the liver (24) and an increase in its biosynthesis (25). Recent data indicate that women with primary hypothyroidism need a higher T 4 dose when under estrogen treatment (26).…”

Thyroid Function Tests During First-trimester of Pregnancy: A Review of Literature

“…This physiological process, modify the T4 basic point which can be focused on hypothyroid concentration. and total thyroxin level increased at early patients is the level of lipid per-oxidations and free radical stage of first-trimester of pregnancy (Ain et al, 1987; productions which can cause tissue injury and other Kumar et al, 2003;Shahmohammdi et al, 2008). abnormality.…”

Autoimmune Thyroid Disease in Pregnancy: A Review

“…As a consequence, by week 10 of gestation, total T 4 and T 3 serum concentrations are increased and plateau at this level until delivery. 4,5 Other physiological adjustments also increase TH synthesis, such as elevation in the maternal glomerular filtration rate (GFR) and transplacental passage of T 4 . 6 These changes mean that adjusted normal reference ranges for thyroid function tests, unique to pregnancy, must be consulted ( Figs.…”