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.
","abstract_html":"<p>Dosage dependent binding inhibition and redistribution of thyroxine (T<sub>4</sub>) 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 T<sub>4</sub>.</p> <p>Furosemide (1.0 mol/L) reduced TBG bound T<sub>4</sub> in both the TBG-TTR system and TBG-albumin system (>90% decrease) and inhibited T<sub>4</sub> binding to TTR in the TTR-albumin system (68% decrease) and to albumin in the TBG-albumin system (44% decrease). T<sub>4</sub> binding inhibition at 1.0 mol/L furosemide was accompanied by increases in free T<sub>4</sub> (FT<sub>4</sub>) : TBG-TTR system, 1063%; TBG-albumin system, 220%; and TTR-Albumin system, 334%.</p> <p>Oleic Acid had no effect on T<sub>4</sub> binding to TBG in the TBG-TTR system, and minimal effect on T<sub>4</sub> binding to TBG in the TBG-albumin system, Significant inhibition of T<sub>4</sub> 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-T<sub>4</sub> binding was inhibited in the TTR-albumin system. FT<sub>4</sub> increased in response to inhibition of binding at 0.10 mol/L in all oleic acid assays.</p> <p>Repartitioning of T<sub>4</sub> between T<sub>4</sub> binding proteins occurred with both furosemide and oleic acid. In the furosemide assays, a decrease in TBG bound T<sub>4</sub> (38%) was coupled with an increase in TTR bound T<sub>4</sub> (29%) in the TBG-TTR system at 1.0 mol/L furosemide. In the TTR-albumin system, a concurrent decrease in TTR bound T<sub>4</sub> (68%) and increase in albumin bound T<sub>4</sub> (67%) was observed at 1.0 mol/L furosemide. Repartitioning of [<sup><sub>125</sub></sup>I]T<sub>4</sub> between binding proteins by oleic acid was observed in the TBG-albumin system by a 3% decline in TBG bound T<sub>4</sub> and 64% increase in albumin bound T<sub>4</sub> at 0.10 mol/L oleic acid.</p> <p>These data confirm that furosemide and oleic acid are potent inhibitors of T<sub>4</sub> binding to purified serum proteins <em>in vitro</em>. Increases in FT<sub>4</sub> concentrations resulting from displacement of T<sub>4</sub> 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 T<sub>4</sub> only from TTR and albumin suggests that oleic acid cannot generate the inhibition of T<sub>4</sub> binding to TBG characteristic of NTI.</p>","abstract_has_math":false,"creators":["Hustead, Deborah"],"institution":null,"degree_name":"Master of Science (MS)","degree_level":"Thesis","degree_discipline":"Biology","degree_department":null,"school":null,"contributors":["R. Bruce Wilcox","Leonard R. Brand","David L. Cowles","Jerald C. Nelson"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":1994,"date_issued":"1994-08-01T07:00:00Z","date_published":"1994-08-01T07:00:00Z","updated_at":"2026-07-24T02:54:01Z","subjects":["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"],"languages":["English"],"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."],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://scholarsrepository.llu.edu/etd/1503","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["R. Bruce Wilcox","Leonard R. Brand","David L. Cowles","Jerald C. Nelson"]},{"key":"dc:creator","label":"Author","values":["Hustead, Deborah"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"thesis:degree_discipline","label":"Discipline","values":["Biology"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Thesis"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Master of Science (MS)"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["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"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["English"]},{"key":"dc:rights","label":"Dc Rights","values":["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."]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://scholarsrepository.llu.edu/etd/1503"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["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.
"]},{"key":"dc:title","label":"Title","values":["Effects of Furosemide and Oleic Acid On Thyroxine Binding to Isolated Pairs of Thyroxine Binding Serum Proteins"]}]}],"canonical_facts":{"dc:contributor":["R. Bruce Wilcox","Leonard R. Brand","David L. Cowles","Jerald C. Nelson"],"dc:creator":["Hustead, Deborah"],"dc:description.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.
"],"dc:identifier":["https://scholarsrepository.llu.edu/etd/1503"],"dc:language":["English"],"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."],"dc:subject":["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"],"dc:title":["Effects of Furosemide and Oleic Acid On Thyroxine Binding to Isolated Pairs of Thyroxine Binding Serum Proteins"],"thesis:degree_discipline":["Biology"],"thesis:degree_level":["Thesis"],"thesis:degree_name":["Master of Science (MS)"]},"updated_at":"2026-07-24T02:54:01Z"}