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

Nicole S. Brown, Alexandra Smart, Vibha Sharma, Michelle L. Brinkmeier, Lauren Greenlee, Sally A. Camper, Dalan R. Jensen, Robert H. Eckel, Wojciech Krezel, Pierre Chambon, Bryan R. Haugen

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Abstract

Vitamin A and retinoids affect pituitary-thyroid function through suppression of serum thyroid-stimulating hormone (TSH) levels and TSH-β subunit gene expression. We have previously shown that retinoid X receptor- selective (RXR-selective) ligands can suppress serum TSH levels in vivo and TSH-β promoter activity in vitro. The RXR-γ 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-γ isotype. These mice had significantly higher serum T4 levels and TSH levels than did wild-type (WT) controls. Treatment of RXR-γ-deficient and WT mice with T3 suppressed serum TSH and T4 levels in both groups, but RXR-γ-deficient mice were relatively resistant to exogenous T3. RXR-γ-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-γ, 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-γ 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.

Original languageEnglish (US)
Pages (from-to)73-79
Number of pages7
JournalJournal of Clinical Investigation
Volume106
Issue number1
DOIs
StatePublished - Jul 2000

All Science Journal Classification (ASJC) codes

  • Medicine(all)

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