Specificity of thyroid hormone receptor subtype and steroid receptor coactivator-1 on thyroid hormone action

Peter M. Sadow, Olivier Chassande, Karine Gauthier, Jacques Samarut, Jianming Xu, Bert W. O'Malley, Roy E. Weiss

Research output: Contribution to journalArticle

38 Scopus citations

Abstract

Isoforms of the thyroid hormone receptor (TR)α and TRβ genes mediate thyroid hormone action. How TR isoforms modulate tissue-specific thyroid hormone (TH) action remains largely unknown. The steroid receptor coactivator-1 (SRC-1) is among a group of transcriptional coactivator proteins that bind to TRs, along with other members of the nuclear receptor superfamily, and modulate the activity of genes regulated by TH. Mice deficient in SRC-1 possess decreased tissue responsiveness to TH and many steroid hormones; however, it is not known whether or not SRC-1mediated activation of TH-regulated gene transcription in peripheral tissues, such as heart and liver, is TR isoform specific. We have generated mice deficient in TRα and SRC-1, as well as in TRβ and SRC-1, and investigated thyroid function tests and effects of TH deprivation and TH treatment compared with wild-type (WT) mice or those deficient in either TR or SRC-1 alone. The data show that 1) in the absence of TRα or TRβ, SRC-1 is important for normal growth; 2) SRC-1 modulates TRα and TRβ effects on heart rate; 3) two new TRβ-dependent markers of TH action in the liver have been identified, osteopontin (upregulated) and glutathione S-transferase (downregulated); and 4) SRC-1 may mediate the hypersensitivity to TH seen in liver of TRβ-deficient mice.

Original languageEnglish (US)
Pages (from-to)E36-E46
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume284
Issue number1 47-1
StatePublished - Jan 1 2003
Externally publishedYes

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Keywords

  • Knockout
  • Resistance to thyroid hormone
  • Thyrotropin

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)

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