Abstract

Dosage dependent binding inhibition and redistribution of thyroxine (T4) between three pairs of thyroxine binding serum proteins, TBG-TTR, TBG-albumin and TTR-albumin, by furosemide (0.0 to 1.0 mol/L) and oleic acid (0.0 to 0.10 mol/L) were studied using equilibrium dialysis with purified binding proteins at concentrations 1/200 of levels in normal human sera, separated across the dialysis membrane and competing for T4.

Furosemide (1.0 mol/L) reduced TBG bound T4 in both the TBG-TTR system and TBG-albumin system (>90% decrease) and inhibited T4 binding to TTR in the TTR-albumin system (68% decrease) and to albumin in the TBG-albumin system (44% decrease). T4 binding inhibition at 1.0 mol/L furosemide was accompanied by increases in free T4 (FT4) : TBG-TTR system, 1063%; TBG-albumin system, 220%; and TTR-Albumin system, 334%.

Oleic Acid had no effect on T4 binding to TBG in the TBG-TTR system, and minimal effect on T4 binding to TBG in the TBG-albumin system, Significant inhibition of T4 binding to TTR was observed in the TBG-TTR (47% decrease) and TTR-albumin (59% decrease) systems at 0.10 mol/L oleic acid concentration. Albumin-T4 binding was inhibited in the TTR-albumin system. FT4 increased in response to inhibition of binding at 0.10 mol/L in all oleic acid assays.

Repartitioning of T4 between T4 binding proteins occurred with both furosemide and oleic acid. In the furosemide assays, a decrease in TBG bound T4 (38%) was coupled with an increase in TTR bound T4 (29%) in the TBG-TTR system at 1.0 mol/L furosemide. In the TTR-albumin system, a concurrent decrease in TTR bound T4 (68%) and increase in albumin bound T4 (67%) was observed at 1.0 mol/L furosemide. Repartitioning of [125I]T4 between binding proteins by oleic acid was observed in the TBG-albumin system by a 3% decline in TBG bound T4 and 64% increase in albumin bound T4 at 0.10 mol/L oleic acid.

These data confirm that furosemide and oleic acid are potent inhibitors of T4 binding to purified serum proteins in vitro. Increases in FT4 concentrations resulting from displacement of T4 from proteins occurred above physiologic concentrations of oleic acid in the TBG-TTR, TBG-albumin, and TTR-albumin systems. The finding that oleic acid displaced T4 only from TTR and albumin suggests that oleic acid cannot generate the inhibition of T4 binding to TBG characteristic of NTI.

LLU Discipline

Biology

Department

Biology

School

Graduate School

First Advisor

R. Bruce Wilcox

Second Advisor

Leonard R. Brand

Third Advisor

David L. Cowles

Fourth Advisor

Jerald C. Nelson

Degree Name

Master of Science (MS)

Degree Level

M.S.

Year Degree Awarded

1994

Date (Title Page)

8-1994

Language

English

Library of Congress/MESH Subject Headings

Thyroxine-Binding Proteins; Furosemide; Oleic Acids

Type

Thesis

Page Count

v; 41

Digital Format

PDF

Digital Publisher

Loma Linda University Libraries

Usage Rights

This title appears here courtesy of the author, who has granted Loma Linda University a limited, non-exclusive right to make this publication available to the public. The author retains all other copyrights.

Collection

Loma Linda University Electronic Theses and Dissertations

Collection Website

http://scholarsrepository.llu.edu/etd/

Repository

Loma Linda University. Del E. Webb Memorial Library. University Archives

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