Reduced clearance rate of thyroxine-binding globulin (TBG) with increased sialylation: A mechanism for estrogen-induced elevation of serum TBG concentration

Kenneth B. Ain, Yuichi Mori, Samuel Refetoff

Research output: Contribution to journalArticlepeer-review

226 Scopus citations

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 (t½) 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 t½. TBG in serum from a pregnant woman had a significantly longer t½ 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 t½ 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 t½ values. Neither the TBG concentration nor estrogen had a direct effect on the rate of TBG clearance. Indeed, the t½ 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.

Original languageEnglish
Pages (from-to)689-696
Number of pages8
JournalJournal of Clinical Endocrinology and Metabolism
Volume65
Issue number4
DOIs
StatePublished - Oct 1987

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

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