Thyroid hormone receptor-specific interactions with steroid receptor coactivator-1 in the pituitary

Peter M. Sadow, Eugene Koo, Olivier Chassande, Karine Gauthier, Jacques Samarut, Jianming Xu, Bert W. O'Malley, Hisao Seo, Yoshiharu Murata, Roy E. Weiss

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

Steroid receptor coactivator-1 (SRC-1) is a transcription cofactor that enhances the hormone-dependent action mediated by the thyroid hormone (TH) receptor (TR) as well as other nuclear receptors. However, it is not known whether the SRC-1-mediated activation of TH-regulated gene transcription is TR isoform specific in the pituitary. We generated mice that were deficient in TRα and SRC-1 (TRα0/0SRC-1-/-), as well in TRβ and SRC-1 (TRβ-/-SRC-1-/-), and thyroid function tests and effects of TH deprivation and TH treatment were compared with wild-type mice or mice with deletion of either TRs or SRC-1 alone. We have shown that 1) TRβ-/-SRC-1-/- mice demonstrate more severe TH resistance than either the SRC-1-/- or TRβ-/- mice; the additive effect indicates that SRC-1 has an independent role in TH action over that of TRβ; 2) SRC-1 facilitates TRβ and TRα-mediated down-regulation of TSH, as TRα0/0SRC-1-/- mice demonstrate TH resistance rather than hypersensitivity as seen in TRα0/0 mice; and 3) a compensatory increase in SRC-1 expression is associated with the TH hypersensitivity seen in TRα-deficient animals. We conclude that SRC-1 action in the pituitary mediates TH action via specific TR subtypes.

Original languageEnglish (US)
Pages (from-to)882-894
Number of pages13
JournalMolecular Endocrinology
Volume17
Issue number5
DOIs
StatePublished - May 1 2003
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology

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    Sadow, P. M., Koo, E., Chassande, O., Gauthier, K., Samarut, J., Xu, J., O'Malley, B. W., Seo, H., Murata, Y., & Weiss, R. E. (2003). Thyroid hormone receptor-specific interactions with steroid receptor coactivator-1 in the pituitary. Molecular Endocrinology, 17(5), 882-894. https://doi.org/10.1210/me.2002-0174