Thyroid hormone resistance and increased metabolic rate in the RXR-gamma-deficient mouse.
J Clin Invest
; 106(1): 73-9, 2000 Jul.
Article
en En
| MEDLINE
| ID: mdl-10880050
ABSTRACT
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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Factores de Transcripción
/
Receptores de Ácido Retinoico
/
Síndrome de Resistencia a Hormonas Tiroideas
/
Metabolismo Energético
Límite:
Animals
Idioma:
En
Revista:
J Clin Invest
Año:
2000
Tipo del documento:
Article
País de afiliación:
Estados Unidos