Differential Binding of Thyroxine and Triiodothyronine to Acidic Isoforms of Thyroid Hormone Binding Globulin in Human Serum

Tetsuya Terasaki, William M. Pardridge

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8 Citations (Scopus)

Abstract

The differential availability of thyroxine (T4) and 3,5,3′-triiodothyronine (T3) to liver from the circulating thyroid hormone binding globulin (TBG)-bound pool suggests that the two thyroid hormones may bind to different TBG isoforms in human serum. In the present study, the binding of [125I]T4and [125I]T3to human serum proteins was investigated by using slab gel isoelectric focusing and chromatofocusing. In normal human male serum, [125I]T4was localized to four isoforms of TBG called TBG-I, -II, -III, and -IV, with isoelectric points (p/'s) of 4.30, 4.35, 4.45, and 4.55, respectively. [125I]T3was localized to only two isoforms of TBG, TBG-III and -IV, with p/′s that were identical with those for [125I]T4. In normal female serum, [125I]T4was localized to the same four isoforms of TBG as those of normal male serum, while [125I]T3was localized to TBG-II, -III, -IV, and -V (pI = 4.65). In pregnant female serum, [125I]T4was localized to five isoforms, whereas [125I]T3was localized to four. IEF was also performed with male serum loaded with various concentrations of unlabeled T3. the Kivalues of T3binding to TBG-I, -II, -III, and -IV were 5.0, 2.4, 0.86, and 0.46 nM, respectively. the TBG isoforms in normal male serum were also separated by sequential concanavalin A-Sepharose affinity chromatography and chromatofocusing (pH range of 3.5-5.0). T4preferentially bound to the most acidic isoforms of TBG in the pI range of 3.8-4.0, whereas the less acidic fractions (pH 4.0-4.2) bound both T4and T3. In conclusion, this study shows that T4and T3do not bind to a single competitive binding site on TBG. Instead, T4is preferentially bound by the most acidic TBG isoforms owing to a 10-fold lower affinity of T3for these proteins.

Original languageEnglish
Pages (from-to)3624-3628
Number of pages5
JournalBiochemistry
Volume27
Issue number10
DOIs
Publication statusPublished - 1988 May 1

ASJC Scopus subject areas

  • Biochemistry

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