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

Mol Endocrinol. 2003 May;17(5):882-94. doi: 10.1210/me.2002-0174. Epub 2003 Feb 6.


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 TRalpha and SRC-1 (TRalpha(0/0)SRC-1(-/-)), as well in TRbeta and SRC-1 (TRbeta(-/-)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) TRbeta(-/-)SRC-1(-/-) mice demonstrate more severe TH resistance than either the SRC-1(-/-) or TRbeta(-/-) mice; the additive effect indicates that SRC-1 has an independent role in TH action over that of TRbeta; 2) SRC-1 facilitates TRbeta and TRalpha-mediated down-regulation of TSH, as TRalpha(0/0)SRC-1(-/-) mice demonstrate TH resistance rather than hypersensitivity as seen in TRalpha(0/0)mice; and 3) a compensatory increase in SRC-1 expression is associated with the TH hypersensitivity seen in TRalpha-deficient animals. We conclude that SRC-1 action in the pituitary mediates TH action via specific TR subtypes.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Nucleus / metabolism
  • Female
  • Histone Acetyltransferases
  • Male
  • Mice
  • Mice, Mutant Strains
  • Nuclear Receptor Coactivator 1
  • Nuclear Receptor Coactivator 2
  • Nuclear Receptor Coactivator 3
  • Pituitary Gland / drug effects
  • Pituitary Gland / physiology*
  • RNA, Messenger / drug effects
  • Receptors, Thyroid Hormone / genetics
  • Receptors, Thyroid Hormone / metabolism*
  • Thyroid Function Tests
  • Thyroid Hormone Receptors alpha / genetics
  • Thyroid Hormone Receptors alpha / metabolism*
  • Thyroid Hormone Receptors beta
  • Thyroid Hormone Resistance Syndrome / drug therapy
  • Thyroid Hormone Resistance Syndrome / genetics
  • Thyroid Hormone Resistance Syndrome / metabolism
  • Thyroid Hormones / deficiency
  • Thyroid Hormones / metabolism
  • Thyroid Hormones / pharmacology
  • Thyrotropin / blood
  • Thyrotropin / genetics
  • Thyrotropin / metabolism
  • Thyrotropin, beta Subunit / drug effects
  • Thyrotropin, beta Subunit / genetics
  • Trans-Activators / genetics
  • Trans-Activators / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Triiodothyronine / metabolism


  • Nuclear Receptor Coactivator 2
  • RNA, Messenger
  • Receptors, Thyroid Hormone
  • Thyroid Hormone Receptors alpha
  • Thyroid Hormone Receptors beta
  • Thyroid Hormones
  • Thyrotropin, beta Subunit
  • Trans-Activators
  • Transcription Factors
  • Triiodothyronine
  • Thyrotropin
  • Histone Acetyltransferases
  • Ncoa1 protein, mouse
  • Ncoa3 protein, mouse
  • Nuclear Receptor Coactivator 1
  • Nuclear Receptor Coactivator 3