Thyroid hormone receptor α and regulation of type 3 deiodinase

Olga Barca-Mayo, Xiao Hui Liao, Manuela Alonso, Caterina di Cosmo, Arturo Hernandez, Samuel Refetoff, Roy E. Weiss

Research output: Contribution to journalArticle

42 Scopus citations

Abstract

Mice deficient in thyroid hormone receptor α (TRα) display hypersensitivity to thyroid hormone (TH), with normal serum TSH but diminished serum T4. Our aim was to determine whether altered TH metabolism played a role in this hypersensitivity. TRα knockout (KO) mice have lower levels of rT3, and lower rT3/T4 ratios compared with wild-type (WT) mice. These alterations could be due to increased type 1 deiodinase (D1) or decreased type 3 deiodinase (D3).Nodifferences in D1mRNAexpression and enzymatic activity were found between WT and TRαKO mice. We observed that T3 treatment increased D3 mRNA in mouse embryonic fibroblasts obtained from WT or TRαKO mice, but not in those from TRαKO mice. T3 stimulated the promoter activity of 1.5 kb 5'-flanking region of the human (h) DIO3 promoter inGH3cells after cotransfection with hTRα but not with hTRα. Moreover, treatment of GH3 cells with T3 increased D3mRNAafter overexpression of TRα. The region necessary for the T3-TRα stimulation of the hD3 promoter (region-1200 to-1369) was identified by transfection studies in Neuro2A cells that stably overexpress either TRα or TRβ. These results indicate that TRα mediates the up-regulation of D3 by TH in vitro. TRαKO mice display impairment in the regulation of D3 by TH in both brain and pituitary and have reduced clearance rate of TH as a consequence of D3 deregulation. Weconclude that the absence of TRα results in decreased clearance of TH by D3 and contributes to the TH hypersensitivity.

Original languageEnglish (US)
Pages (from-to)575-583
Number of pages9
JournalMolecular Endocrinology
Volume25
Issue number4
DOIs
StatePublished - Apr 2011

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology

Fingerprint Dive into the research topics of 'Thyroid hormone receptor α and regulation of type 3 deiodinase'. Together they form a unique fingerprint.

  • Cite this

    Barca-Mayo, O., Liao, X. H., Alonso, M., di Cosmo, C., Hernandez, A., Refetoff, S., & Weiss, R. E. (2011). Thyroid hormone receptor α and regulation of type 3 deiodinase. Molecular Endocrinology, 25(4), 575-583. https://doi.org/10.1210/me.2010-0213