Functional significance of a truncated thyroid receptor subtype lacking a hormone-binding domain in goldfish

Erik R. Nelson, Hamid R. Habibi

Research output: Contribution to journalArticle

Abstract

Thyroid hormones are important mediators of growth and development in vertebrates and act by binding to a specific family of thyroid receptors (TRs). The TRs belong to the nuclear receptor superfamily, with two conserved regions, a DNA binding domain and a ligand binding domain (LBD). We recently demonstrated the presence of four TR subtypes in goldfish, two with complete DNA binding domains and LBDs (TRα-1 and TRβ) and two novel forms including a transcript resembling TRα with variation in the LBD as well as a TRα-truncated (TRα-t) form lacking a LBD. To study the functional significance of TR subtypes, we first investigated the regulation of hepatic goldfish deiodinase type 3 (D3) by T3 and validated a bioassay in which D3 gene expression is up-regulated significantly in vivo and in vitro. Using short interfering RNA, TRα-1, TRβ, or TRα-t was specifically knocked down and thyroid hormone-induced D3 gene expression was measured. short interfering RNA against TRα-1 or TRβ reduced the T3 induction of deiodinase gene expression to 50% or less than 25% of control (T3 treated) cells, respectively. Knocking down TRα-t alone, however, increased D3 expression 500-fold supporting the hypothesis that TRα-t plays a modulatory role in thyroid hormone-induced gene expression. Our results provide important insight into thyroid receptor biology in goldfish and a framework for the better understanding of thyroid receptor function in all vertebrates.

Original languageEnglish (US)
Pages (from-to)4702-4709
Number of pages8
JournalEndocrinology
Volume149
Issue number9
DOIs
StatePublished - Sep 1 2008
Externally publishedYes

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Goldfish
Thyroid Gland
Hormones
Iodide Peroxidase
Thyroid Hormones
Gene Expression
Ligands
Small Interfering RNA
Vertebrates
Thyroid Hormone Receptors
DNA
Cytoplasmic and Nuclear Receptors

ASJC Scopus subject areas

  • Endocrinology

Cite this

Functional significance of a truncated thyroid receptor subtype lacking a hormone-binding domain in goldfish. / Nelson, Erik R.; Habibi, Hamid R.

In: Endocrinology, Vol. 149, No. 9, 01.09.2008, p. 4702-4709.

Research output: Contribution to journalArticle

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