Mice deficient in the steroid receptor co-activator 1 (SRC-1) are resistant to thyroid hormone

Roy E Weiss, Jianming Xu, Guang Ning, Joachim Pohlenz, Bert W. O'Malley, Samuel Refetoff

Research output: Contribution to journalArticle

205 Citations (Scopus)

Abstract

Steroid receptor co-activator 1 (SRC-1) is a transcription co-factor that enhances the hormone-dependent action, mediated by the thyroid hormone (TH) receptor (TR) and other nuclear receptors. In vitro studies have shown that SRC-1 is necessary for the full expression of TH effect. SRC-1 knockout mice (SRC-1(-/-)) provide a model to examine the role of this co-activator on TH action in vivo. At baseline, SRC-1(-/-) mice display resistance to TH (RTH) as evidenced by a 2.5-fold elevation of serum TSH levels, despite a 50% increase in serum free TH levels as compared with wild-type (SRC-1(+/+)) mice. When mice were made hypothyroid, TSH levels increased, obliterating the difference between SRC-1(+/+) and SRC-1(-/-) mice observed at baseline. In contrast, the decline of TSH by treatment with L-triiodothyronine was severely blunted in SRC-1(-/-) mice. These data indicate that SRC-1 is not required for the upregulation of TSH in TH deficiency. However, SRC-1 enhances the sensitivity of TSH downregulation by TH. This is the first demonstration of RTH caused by a deficient co-factor other than TR. It supports the hypothesis that a putative defect in the SRC-1 gene or another co-factor could be the cause of RTH in humans without mutations in the TR genes.

Original languageEnglish (US)
Pages (from-to)1900-1904
Number of pages5
JournalEMBO Journal
Volume18
Issue number7
StatePublished - Apr 1 1999
Externally publishedYes

Fingerprint

Steroid Receptors
Thyroid Hormones
Genes
Thyroid Hormone Resistance Syndrome
Thyroid Hormone Receptors
Triiodothyronine
Transcription
Cytoplasmic and Nuclear Receptors
Serum
Knockout Mice
Transcription Factors
Up-Regulation
Demonstrations
Down-Regulation
Hormones

Keywords

  • Co-activator
  • Resistance to thyroid hormone
  • SRC-1
  • Thyroid hormone receptor
  • Thyrotropin

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

Cite this

Weiss, R. E., Xu, J., Ning, G., Pohlenz, J., O'Malley, B. W., & Refetoff, S. (1999). Mice deficient in the steroid receptor co-activator 1 (SRC-1) are resistant to thyroid hormone. EMBO Journal, 18(7), 1900-1904.

Mice deficient in the steroid receptor co-activator 1 (SRC-1) are resistant to thyroid hormone. / Weiss, Roy E; Xu, Jianming; Ning, Guang; Pohlenz, Joachim; O'Malley, Bert W.; Refetoff, Samuel.

In: EMBO Journal, Vol. 18, No. 7, 01.04.1999, p. 1900-1904.

Research output: Contribution to journalArticle

Weiss, RE, Xu, J, Ning, G, Pohlenz, J, O'Malley, BW & Refetoff, S 1999, 'Mice deficient in the steroid receptor co-activator 1 (SRC-1) are resistant to thyroid hormone', EMBO Journal, vol. 18, no. 7, pp. 1900-1904.
Weiss RE, Xu J, Ning G, Pohlenz J, O'Malley BW, Refetoff S. Mice deficient in the steroid receptor co-activator 1 (SRC-1) are resistant to thyroid hormone. EMBO Journal. 1999 Apr 1;18(7):1900-1904.
Weiss, Roy E ; Xu, Jianming ; Ning, Guang ; Pohlenz, Joachim ; O'Malley, Bert W. ; Refetoff, Samuel. / Mice deficient in the steroid receptor co-activator 1 (SRC-1) are resistant to thyroid hormone. In: EMBO Journal. 1999 ; Vol. 18, No. 7. pp. 1900-1904.
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