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

Inna Astapova1, Kristen R Vella, Preeti Ramadoss

  • 1Division of Endocrinology, Diabetes, and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachsetts 02215, USA. iastapov@bidmc.harvard.edu

Molecular Endocrinology (Baltimore, Md.)
|January 18, 2011
PubMed

Insights

Nuclear receptor corepressor (NCoR) is crucial for thyroid hormone (TH) action. Disrupting NCoR-TR interaction reveals NCoR

Area of Science:

  • Endocrinology
  • Molecular Biology
  • Genetics

Background:

  • Thyroid hormone (TH) regulates metabolism and development.
  • Nuclear receptor corepressor (NCoR) is a key regulator of nuclear receptor activity.
  • Global NCoR deletion is embryonic lethal, hindering study of its role in TH action.

Purpose of the Study:

  • To investigate the role of NCoR in thyroid hormone (TH) action using a novel mouse model.
  • To understand how NCoR-TR interaction influences systemic TH sensitivity and the hypothalamic-pituitary-thyroid (HPT) axis.

Main Methods:

  • Generated mice expressing a modified NCoR protein (NCoRΔID) unable to bind the thyroid hormone receptor (TR).
  • Analyzed serum hormone levels (T4, T3, TSH), energy expenditure, and TR-target gene expression.
  • Assessed HPT axis sensitivity and thyroid gland function.

Main Results:

  • NCoRΔID mice exhibited low serum T4/T3 with normal TSH, suggesting central hypothyroidism, but showed normal growth and increased energy expenditure.
  • TR-target gene expression was normal or elevated, indicating increased peripheral TH sensitivity.
  • The HPT axis set point was reset, and the thyroid gland showed reduced responsiveness to TSH.

Conclusions:

  • The TR-NCoR interaction is critical for regulating systemic TH sensitivity and the HPT axis set point.
  • NCoR influences cell-specific TH action independently of serum TSH levels.
  • Targeting NCoR could modulate TH action in various tissues.

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