Thyroid hormone receptors. Alteration of hormone-binding specificity

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

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

In previous studies of nuclear extracts containing solubilized receptors for thyroid hormones, triiodothyronine (T 3) but not thyroxine (T 4) binding activity was lost, even though in the starting material T 3 and T 4 appeared to bind to the same proteins. In the current studies this paradoxical loss of T 3 but not T 4 binding activity was studied in greater detail. Competition, iodoacetamide inhibition and binding site concentration studies with [ 125I]T 3 and [ 125I]T 4 were consistent with the idea that T 3 and T 4 are bound by the same protein(s) in the initial extracts. When such preparations were heated at 50°C, [ 125I]T 3 but not [ 125I)T 4 binding activity was rapidly lost. There was no change in the T 4 binding site concentration and no change or a modest reduction in affinity. By contrast, heating markedly reduced the concentration of high affinity T 3 binding sites; the affinity of the remaining sites for T 3 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 T 3 binding site concentration was markedly reduced but the T 4 binding site concentration and affinity were minimally affected. T 3 was a more avid competitor than T 4 for [ 125I]T 4 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 T 4-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 T 4, but which has reduced affinity for T 3; in this case a fundamental unit of the receptor could be more similar than previously apparent to certain cytosol or plasma proteins than bind T 4 more avidly than T 3.

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

    Fingerprint

ASJC Scopus subject areas

  • Biochemistry

Cite this

Eberhardt, N. L., Ring, J. C., Latham, K. R., & Baxter, J. D. (1979). Thyroid hormone receptors. Alteration of hormone-binding specificity. Journal of Biological Chemistry, 254(17), 8534-8539.