Binding of selected iodothyronine analogues to receptor sites of isolated rat hepatic nuclei. High correlation between structural requirements for nuclear binding and biological activity

D. Koerner, H. L. Schwartz, Martin I. Surks, J. H. Oppenheimer

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Abstract

The limited capacity, high affinity binding of 35 iodothyronine analogues by rat liver nuclei has been examined in an in vitro system. The in vitro nuclear binding of all the analogues tested was highly correlated with their published thyromimetic potencies in the intact animals. Binding and biological activity are greater for 3' mono than 3',5' di substituted iodothyronines. A 4' hydroxyl group is essential, but the 3' substituent can be several halogen or non halogen groups for which the distal conformation is preferred. The ether linkage can be replaced equally well by a methylene or sulfur group. The presence of both 3 and 5 groups which are limited to halogens or small alkyl groups are necessary for the maintenance of significant activity. Halogen free iodothyronines have very low, but significant activity both in vitro and in vivo. The data provide information on the structural requirements for thyroid hormone action and further support the physiological relevance of the nuclear sites.

Original languageEnglish (US)
Pages (from-to)6417-6423
Number of pages7
JournalJournal of Biological Chemistry
Volume250
Issue number16
StatePublished - 1975

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Halogens
Bioactivity
Rats
Liver
Thyroid Hormones
Sulfur
Hydroxyl Radical
Ether
Conformations
Animals
Maintenance
In Vitro Techniques

ASJC Scopus subject areas

  • Biochemistry

Cite this

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abstract = "The limited capacity, high affinity binding of 35 iodothyronine analogues by rat liver nuclei has been examined in an in vitro system. The in vitro nuclear binding of all the analogues tested was highly correlated with their published thyromimetic potencies in the intact animals. Binding and biological activity are greater for 3' mono than 3',5' di substituted iodothyronines. A 4' hydroxyl group is essential, but the 3' substituent can be several halogen or non halogen groups for which the distal conformation is preferred. The ether linkage can be replaced equally well by a methylene or sulfur group. The presence of both 3 and 5 groups which are limited to halogens or small alkyl groups are necessary for the maintenance of significant activity. Halogen free iodothyronines have very low, but significant activity both in vitro and in vivo. The data provide information on the structural requirements for thyroid hormone action and further support the physiological relevance of the nuclear sites.",
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T1 - Binding of selected iodothyronine analogues to receptor sites of isolated rat hepatic nuclei. High correlation between structural requirements for nuclear binding and biological activity

AU - Koerner, D.

AU - Schwartz, H. L.

AU - Surks, Martin I.

AU - Oppenheimer, J. H.

PY - 1975

Y1 - 1975

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AB - The limited capacity, high affinity binding of 35 iodothyronine analogues by rat liver nuclei has been examined in an in vitro system. The in vitro nuclear binding of all the analogues tested was highly correlated with their published thyromimetic potencies in the intact animals. Binding and biological activity are greater for 3' mono than 3',5' di substituted iodothyronines. A 4' hydroxyl group is essential, but the 3' substituent can be several halogen or non halogen groups for which the distal conformation is preferred. The ether linkage can be replaced equally well by a methylene or sulfur group. The presence of both 3 and 5 groups which are limited to halogens or small alkyl groups are necessary for the maintenance of significant activity. Halogen free iodothyronines have very low, but significant activity both in vitro and in vivo. The data provide information on the structural requirements for thyroid hormone action and further support the physiological relevance of the nuclear sites.

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