Comparison of the metabolism and distribution of L-triiodothyronine and triiodothyroacetic acid in the rat

a possible explanation of differential hormonal potency

B. Goslings, H. L. Schwartz, W. Dillmann, Martin I. Surks, J. H. Oppenheimer

Research output: Contribution to journalArticle

64 Citations (Scopus)

Abstract

Previous studies have shown that nuclear displacement of triiodothyronine (T 3) is more rapidly dissipated after iv injection of triiodothyroacetic acid (triac) than after equimolar doses of T 3. This suggested that the discrepancy between the strong nuclear binding of triac and its relatively weak thyromimetic effect could be explained by a more rapid fractional rate of triac metabolism. To test this hypothesis, tracer studies with radioactively labeled T 3 and triac were carried out in normal male Sprague Dawley rats. Noncompartmental analysis showed that the average residence time of tracer triac in the exchangeable compartment was 5.5 h compared with 10.9 h for T 3. The metabolic clearance rate of triac was 14.4 ml/h/100 g BW and of T 3 17.6 ml/h/100 g. The average distribution space of triac was 78.2 ml/100 g and of T 3 190.7 ml/100 g. The fraction of isotope excreted via the fecal route was 0.46 for triac and 0.41 for T 3. Triac was approximately 16 times as firmly bound to plasma proteins as was T 3. Isotopic studies suggested that a rapid exchange of tracer triac occurred between plasma, cytosol, and nuclei, similar to previously observed relationships for T 3. Based on the daily dose of T 3 and triac required to maintain a normal concentration of alpha glycerophosphate dehydrogenase in thyroidectomized animals, the T 3:triac potency ratio was estimated to be 3.0. Our observations support the concept that a shorter duration of nuclear occupancy observed in previous experiments can be attributed to a more rapid fractional metabolism of triac and may explain the lesser hormonal effect of this compound. Since labeled triac could not be identified in nuclear extracts after the injection of isotopically labeled T 3, it appears unlikely that the initiation of hormonal effects by T 3 at the nuclear level is dependent on its prior conversion to triac.

Original languageEnglish (US)
Pages (from-to)666-675
Number of pages10
JournalEndocrinology
Volume98
Issue number3
StatePublished - 1976

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Triiodothyronine
Acids
Metabolic Clearance Rate
Glycerolphosphate Dehydrogenase
Injections
Isotopes
Cytosol
Sprague Dawley Rats
Blood Proteins

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Comparison of the metabolism and distribution of L-triiodothyronine and triiodothyroacetic acid in the rat : a possible explanation of differential hormonal potency. / Goslings, B.; Schwartz, H. L.; Dillmann, W.; Surks, Martin I.; Oppenheimer, J. H.

In: Endocrinology, Vol. 98, No. 3, 1976, p. 666-675.

Research output: Contribution to journalArticle

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