The nuclear receptor corepressor (NCoR) controls thyroid hormone sensitivity and the set point of the hypothalamic-pituitary-thyroid axis

Inna Astapova, Kristen R. Vella, Preeti Ramadoss, Kaila A. Holtz, Benjamin A. Rodwin, Xiao Hui Liao, Roy E. Weiss, Michael A. Rosenberg, Anthony Rosenzweig, Anthony N. Hollenberg

Research output: Contribution to journalArticlepeer-review

60 Scopus citations

Abstract

The role of nuclear receptor corepressor (NCoR) in thyroid hormone (TH) action has been difficult to discern because global deletion of NCoR is embryonic lethal. To circumvent this, we developed mice that globally express a modified NCoR protein (NCoRΔID) that cannot be recruited to the thyroid hormone receptor (TR). These mice present with low serum T4 and T3 concentrations accompanied by normal TSH levels, suggesting central hypothyroidism. However, they grow normally and have increased energy expenditure and normal or elevated TR-target gene expression across multiple tissues, which is not consistent with hypothyroidism. Although these findings imply an increased peripheral sensitivity to TH, the hypothalamic-pituitary- thyroid axis is not more sensitive to acute changes in TH concentrations but appears to be reset to recognize the reduced TH levels as normal. Furthermore, the thyroid gland itself, although normal in size, has reduced levels of nonthyroglobulin-bound T4 and T3 and demonstrates decreased responsiveness to TSH. Thus, the TR-NCoR interaction controls systemic TH sensitivity as well as the set point at all levels of the hypothalamic-pituitary-thyroid axis. These findings suggest that NCoR levels could alter cell-specific TH action that would not be reflected by the serum TSH.

Original languageEnglish (US)
Pages (from-to)212-224
Number of pages13
JournalMolecular Endocrinology
Volume25
Issue number2
DOIs
StatePublished - Feb 2011
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology

Fingerprint

Dive into the research topics of 'The nuclear receptor corepressor (NCoR) controls thyroid hormone sensitivity and the set point of the hypothalamic-pituitary-thyroid axis'. Together they form a unique fingerprint.

Cite this