title: Thyroid hormone resistance and increased metabolic rate in the RXR-gamma-deficient mouse.
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.
authors.affiliation: Department of Medicine, University of Colorado Health Sciences Center, Denver, Colorado, USA.
authors.forename: N S
authors.initials: NS
authors.lastname: Brown
authors.forename: A
authors.initials: A
authors.lastname: Smart
authors.forename: V
authors.initials: V
authors.lastname: Sharma
authors.forename: M L
authors.initials: ML
authors.lastname: Brinkmeier
authors.forename: L
authors.initials: L
authors.lastname: Greenlee
authors.forename: S A
authors.initials: SA
authors.lastname: Camper
authors.forename: D R
authors.initials: DR
authors.lastname: Jensen
authors.forename: R H
authors.initials: RH
authors.lastname: Eckel
authors.forename: W
authors.initials: W
authors.lastname: Krezel
authors.forename: P
authors.initials: P
authors.lastname: Chambon
authors.forename: B R
authors.initials: BR
authors.lastname: Haugen
mesh_terms: D000818:Animals; D004734:Energy Metabolism; D005260:Female; D051379:Mice; D010641:Phenotype; D010902:Pituitary Gland / Q000473:pathology; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000032:analysis; D018168:Receptors, Retinoic Acid / Q000235:genetics / Q000502:physiology*; D047488:Retinoid X Receptors; D013961:Thyroid Gland / Q000473:pathology; D018382:Thyroid Hormone Resistance Syndrome / Q000378:metabolism*; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000097:blood; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*
chemical_list: D012333:RNA, Messenger; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D014157:Transcription Factors; D013972:Thyrotropin; D013974:Thyroxine