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Title: Differential binding of thyroxine and triiodothyronine to acidic isoforms of thyroid hormone binding globulin in human serum

Abstract

The differential availability of thyroxine (T/sub 4/) and 3,5,3'-triiodothyronine (T/sub 3/) 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 (/sup 125/I)T/sub 4/ and (/sup 125/I)T/sub 3/ to human serum proteins was investigated by using slab gel isoelectric focusing and chromatofocusing. In normal human male serum, (/sup 125/I)T/sub 4/ was localized to four isoforms of TBG called TBG-I, -II, -III, and -IV, with isoelectric points (pI's) of 4.30, 4.35, 4.45, and 4.55, respectively. (/sup 125/I)T/sub 3/ was localized to only two isoforms of TBG, TBG-III, and -IV, with pI's that were identical with those for (/sup 125/I)T/sub 4/. In normal female serum, (/sup 125/I)T/sub 4/ was localized to the same four isoforms of TBG as those of normal male serum, while (/sup 125/I)T/sub 3/ was localized to TBG-II, -III, -IV, and -V (pI = 4.65). In pregnant female serum, (/sup 125/I)T/sub 4/ was localized to five isoforms, whereas (/sup 125/I)T/sub 3/ was localized to four. IEF was also performed with male serum loaded with various concentrations of unlabeled T/sub 3/. The K/sub i/ values of T/submore » 3/ binding 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 the chromatofocusing (pH range of 3.5-5.0). T/sub 4/ preferentially 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 T/sub 4/ and T/sub 3/. In conclusion, this study shows that T/sub 4/ and T/sub 3/ do not bind to a single competitive binding site on TBG. Instead, T/sub 4/ is preferentially bound by the most acidic TBG isoforms owing to a 10-fold lower affinity of T/sub 3/ for these proteins.« less

Authors:
;
Publication Date:
Research Org.:
Univ. of California, Los Angeles (USA)
OSTI Identifier:
7191260
Resource Type:
Journal Article
Journal Name:
Biochemistry; (United States)
Additional Journal Information:
Journal Volume: 27:10
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; 59 BASIC BIOLOGICAL SCIENCES; GLOBULINS; AUTORADIOGRAPHY; CONFIGURATION INTERACTION; THYROXINE; TRIIODOTHYRONINE; BLOOD SERUM; IODINE 125; LIVER; MEN; PREGNANCY; PROTEINS; TRITIUM COMPOUNDS; WOMEN; AMINO ACIDS; ANIMALS; BETA DECAY RADIOISOTOPES; BODY; CARBOXYLIC ACIDS; DAYS LIVING RADIOISOTOPES; DIGESTIVE SYSTEM; ELECTRON CAPTURE RADIOISOTOPES; FEMALES; GLANDS; HORMONES; INTERMEDIATE MASS NUCLEI; IODINE ISOTOPES; ISOTOPES; LABELLED COMPOUNDS; MALES; MAMMALS; MAN; NUCLEI; ODD-EVEN NUCLEI; ORGANIC ACIDS; ORGANIC COMPOUNDS; ORGANIC HALOGEN COMPOUNDS; ORGANIC IODINE COMPOUNDS; ORGANS; PEPTIDE HORMONES; PRIMATES; RADIOISOTOPES; THYROID HORMONES; VERTEBRATES; 550601* - Medicine- Unsealed Radionuclides in Diagnostics; 550201 - Biochemistry- Tracer Techniques

Citation Formats

Terasaki, T, and Pardridge, W M. Differential binding of thyroxine and triiodothyronine to acidic isoforms of thyroid hormone binding globulin in human serum. United States: N. p., 1988. Web. doi:10.1021/bi00410a015.
Terasaki, T, & Pardridge, W M. Differential binding of thyroxine and triiodothyronine to acidic isoforms of thyroid hormone binding globulin in human serum. United States. https://doi.org/10.1021/bi00410a015
Terasaki, T, and Pardridge, W M. 1988. "Differential binding of thyroxine and triiodothyronine to acidic isoforms of thyroid hormone binding globulin in human serum". United States. https://doi.org/10.1021/bi00410a015.
@article{osti_7191260,
title = {Differential binding of thyroxine and triiodothyronine to acidic isoforms of thyroid hormone binding globulin in human serum},
author = {Terasaki, T and Pardridge, W M},
abstractNote = {The differential availability of thyroxine (T/sub 4/) and 3,5,3'-triiodothyronine (T/sub 3/) 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 (/sup 125/I)T/sub 4/ and (/sup 125/I)T/sub 3/ to human serum proteins was investigated by using slab gel isoelectric focusing and chromatofocusing. In normal human male serum, (/sup 125/I)T/sub 4/ was localized to four isoforms of TBG called TBG-I, -II, -III, and -IV, with isoelectric points (pI's) of 4.30, 4.35, 4.45, and 4.55, respectively. (/sup 125/I)T/sub 3/ was localized to only two isoforms of TBG, TBG-III, and -IV, with pI's that were identical with those for (/sup 125/I)T/sub 4/. In normal female serum, (/sup 125/I)T/sub 4/ was localized to the same four isoforms of TBG as those of normal male serum, while (/sup 125/I)T/sub 3/ was localized to TBG-II, -III, -IV, and -V (pI = 4.65). In pregnant female serum, (/sup 125/I)T/sub 4/ was localized to five isoforms, whereas (/sup 125/I)T/sub 3/ was localized to four. IEF was also performed with male serum loaded with various concentrations of unlabeled T/sub 3/. The K/sub i/ values of T/sub 3/ binding 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 the chromatofocusing (pH range of 3.5-5.0). T/sub 4/ preferentially 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 T/sub 4/ and T/sub 3/. In conclusion, this study shows that T/sub 4/ and T/sub 3/ do not bind to a single competitive binding site on TBG. Instead, T/sub 4/ is preferentially bound by the most acidic TBG isoforms owing to a 10-fold lower affinity of T/sub 3/ for these proteins.},
doi = {10.1021/bi00410a015},
url = {https://www.osti.gov/biblio/7191260}, journal = {Biochemistry; (United States)},
number = ,
volume = 27:10,
place = {United States},
year = {Tue May 17 00:00:00 EDT 1988},
month = {Tue May 17 00:00:00 EDT 1988}
}