Thyroid hormone receptors. Alteration of hormone-binding specificity

N. L. Eberhardt, J. C. Ring, K. R. Latham, J. D. Baxter

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

In previous studies of nuclear extracts containing solubilized receptors for thyroid hormones, triiodothyronine (T3) but not thyroxine (T4) binding activity was lost, even though in the starting material T3 and T4 appeared to bind to the same proteins. In the current studies this paradoxical loss of T3 but not T4 binding activity was studied in greater detail. Competition, iodoacetamide inhibition and binding site concentration studies with [125I]T3 and [125I]T4 were consistent with the idea that T3 and T4 are bound by the same protein(s) in the initial extracts. When such preparations were heated at 50°C, [125I]T3 but not [125I)T4 binding activity was rapidly lost. There was no change in the T4 binding site concentration and no change or a modest reduction in affinity. By contrast, heating markedly reduced the concentration of high affinity T3 binding sites; the affinity of the remaining sites for T3 was 0.1% that of the starting material. When the pH of the extract was lowered from 7.6 to 6.0 the high affinity T3 binding site concentration was markedly reduced but the T4 binding site concentration and affinity were minimally affected. T3 was a more avid competitor than T4 for [125I]T4 binding at pH 7.6 but had weak competitor activity at pH 6.0. These heat- and pH-induced influences could occur if the receptors are destroyed and a T4-binding species is generated or exposed. Alternatively, the data can be explained by a model in which the thyroid hormone receptor can be converted to a form which retains binding activity for T4, but which has reduced affinity for T3; in this case a fundamental unit of the receptor could be more similar than previously apparent to certain cytosol or plasma proteins than bind T4 more avidly than T3.

Original languageEnglish (US)
Pages (from-to)8534-8539
Number of pages6
JournalJournal of Biological Chemistry
Volume254
Issue number17
StatePublished - 1979

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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