Thyroid hormone resistance and increased metabolic rate in the RXR-gamma-deficient mouse

J Clin Invest. 2000 Jul;106(1):73-9. doi: 10.1172/JCI9422.


Vitamin A and retinoids affect pituitary-thyroid function through suppression of serum thyroid-stimulating hormone (TSH) levels and TSH-beta subunit gene expression. We have previously shown that retinoid X receptor-selective (RXR-selective) ligands can suppress serum TSH levels in vivo and TSH-beta promoter activity in vitro. The RXR-gamma isotype has limited tissue distribution that includes the thyrotrope cells of the anterior pituitary gland. In this study, we have performed a detailed analysis of the pituitary-thyroid function of mice lacking the gene for the RXR-gamma isotype. These mice had significantly higher serum T4 levels and TSH levels than did wild-type (WT) controls. Treatment of RXR-gamma-deficient and WT mice with T3 suppressed serum TSH and T4 levels in both groups, but RXR-gamma-deficient mice were relatively resistant to exogenous T3. RXR-gamma-deficient mice had significantly higher metabolic rates than did WT controls, suggesting that these animals have a pattern of central resistance to thyroid hormone. RXR-gamma, which is also expressed in skeletal muscle and the hypothalamus, may have a direct effect on muscle metabolism, regulation of food intake, or thyrotropin-releasing hormone levels in the hypothalamus. In conclusion, the RXR-gamma isotype appears to contribute to the regulation of serum TSH and T4 levels and to affect peripheral metabolism through regulation of the hypothalamic-pituitary-thyroid axis or through direct effects on skeletal muscle.

Publication types

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

MeSH terms

  • Animals
  • Energy Metabolism*
  • Female
  • Mice
  • Phenotype
  • Pituitary Gland / pathology
  • Promoter Regions, Genetic
  • RNA, Messenger / analysis
  • Receptors, Retinoic Acid / genetics
  • Receptors, Retinoic Acid / physiology*
  • Retinoid X Receptors
  • Thyroid Gland / pathology
  • Thyroid Hormone Resistance Syndrome / metabolism*
  • Thyrotropin / blood
  • Thyroxine / blood
  • Transcription Factors / genetics
  • Transcription Factors / physiology*


  • RNA, Messenger
  • Receptors, Retinoic Acid
  • Retinoid X Receptors
  • Transcription Factors
  • Thyrotropin
  • Thyroxine