Induction of Larval tissue resorption in Xenopus laevis tadpoles by the thyroid hormone receptor agonist GC-1

John Furlow, Ha Yung Yang, Mei Hsu, Wayland Lim, Davy J. Ermio, Grazia Chiellini, Thomas S. Scanlan

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

A major challenge in understanding nuclear hormone receptor function is to determine how the same ligand can cause very different tissue-specific responses. Tissue specificity may result from the presence of more than one receptor subtype arising from multiple receptor genes or alternative splicing. Recently, high affinity analogs of nuclear receptor ligands have been synthesized that show subtype selectivity. These analogs can greatly facilitate the study of receptor subtype-specific functions in organisms where mutational analysis is problematic or where it is desirable for receptors to be expressed in their normal physiological contexts. We describe here the effects of the synthetic thyroid hormone analog GC-1 on the metamorphosis of the frog Xenopus laevis. The most potent natural thyroid hormone, 3,5,3′-triidothyronine or T3, shows similar binding affinity and transactivation dose-response curves for both thyroid hormone receptor isotypes, designated TRα and TRβ. GC-1, however, binds to and activates TRβ at least an order of magnitude better than it does TRα. GC-1 efficiently induces death and resorption of premetamorphic tadpole tissues such as the gills and the tail, two tissues that strongly induce thyroid hormone receptor β during metamorphosis. GC-1 has less effect on the growth of adult tissues such as the hindlimbs, which express high TRα levels. The effectiveness of GC-1 in inducing tail resorption and tail gene expression correlates with increasing TRβ levels. These results illustrate the utility of subtype selective ligands as probes of nuclear receptor function in vivo.

Original languageEnglish (US)
Pages (from-to)26555-26562
Number of pages8
JournalJournal of Biological Chemistry
Volume279
Issue number25
DOIs
StatePublished - Jun 18 2004

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Thyroid Hormone Receptors
Xenopus laevis
Larva
Hormones
Tissue
Cytoplasmic and Nuclear Receptors
Tail
Ligands
Thyroid Hormones
Organ Specificity
Alternative Splicing
Hindlimb
Gene expression
Anura
Transcriptional Activation
Genes
GC 1 compound
Gene Expression
Growth

ASJC Scopus subject areas

  • Biochemistry

Cite this

Induction of Larval tissue resorption in Xenopus laevis tadpoles by the thyroid hormone receptor agonist GC-1. / Furlow, John; Yang, Ha Yung; Hsu, Mei; Lim, Wayland; Ermio, Davy J.; Chiellini, Grazia; Scanlan, Thomas S.

In: Journal of Biological Chemistry, Vol. 279, No. 25, 18.06.2004, p. 26555-26562.

Research output: Contribution to journalArticle

Furlow, John ; Yang, Ha Yung ; Hsu, Mei ; Lim, Wayland ; Ermio, Davy J. ; Chiellini, Grazia ; Scanlan, Thomas S. / Induction of Larval tissue resorption in Xenopus laevis tadpoles by the thyroid hormone receptor agonist GC-1. In: Journal of Biological Chemistry. 2004 ; Vol. 279, No. 25. pp. 26555-26562.
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