Effects of Furosemide and Oleic Acid On Thyroxine Binding to Isolated Pairs of Thyroxine Binding Serum Proteins

<p>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.</p> <p>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%.</p> <p>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.</p> <p>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.</p> <p>These data confirm that furosemide and oleic acid are potent inhibitors of T₄ binding to purified serum proteins <em>in vitro</em>. 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.</p>

Name thesis:degree_name

Master of Science (MS)

Level thesis:degree_level

Thesis

Discipline thesis:degree_discipline

Biology

Year

1994

Author dc:creator

• Hustead, Deborah

Contributors dc:contributor

• R. Bruce Wilcox
• Leonard R. Brand
• David L. Cowles
• Jerald C. Nelson

• Amino Acids, Peptides, and Proteins
• Biology
• Hormones, Hormone Substitutes, and Hormone Antagonists
• Investigative Techniques
• Laboratory and Basic Science Research
• Thyroxine-Binding Proteins; Furosemide; Oleic Acids

Statement dc: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.

Language dc:language

English

Repository record dc:identifier

https://scholarsrepository.llu.edu/etd/1503

OAI identifier oai:identifier

oai:scholarsrepository.llu.edu:etd-2279