Thyroid hormone resistance and increased metabolic rate in the RXR-gamma-deficient mouse.
Thyroid hormone resistance and increased metabolic rate in the RXR-gamma-deficient mouse.
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发表时间：
2000
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通讯作者：
N. Brown;A. Smart;V. Sharma;M. Brinkmeier;L. Greenlee;S. Camper;D. Jensen;R. Eckel;W. Krężel;P. Chambon;B. Haugen
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作者：
N. Brown;A. Smart;V. Sharma;M. Brinkmeier;L. Greenlee;S. Camper;D. Jensen;R. Eckel;W. Krężel;P. Chambon;B. Haugen
维生素A和类维生素A通过抑制血清促甲状腺激素（TSH）水平和TSH-β亚基基因表达影响垂体-甲状腺功能。我们以前已经表明，类维生素A X受体选择性（RXR选择性）配体可以抑制血清TSH水平在体内和TSH-β启动子活性在体外。RXR-γ同种型具有有限的组织分布，包括垂体前叶的促甲状腺细胞。在这项研究中，我们对缺乏RXR-γ同种型基因的小鼠的垂体-甲状腺功能进行了详细的分析。这些小鼠的血清T4水平和TSH水平显著高于野生型（WT）对照组。用T3治疗RXR-γ缺陷小鼠和WT小鼠，抑制了两组小鼠血清TSH和T4水平，但RXR-γ缺陷小鼠对外源性T3具有相对抗性。RXR-γ缺陷小鼠的代谢率显著高于WT对照组，表明这些动物对甲状腺激素具有中枢抵抗模式。RXR-γ也在骨骼肌和下丘脑中表达，可能对肌肉代谢、食物摄入调节或下丘脑中促甲状腺素释放激素水平有直接影响。总之，RXR-γ同种型似乎有助于调节血清TSH和T4水平，并通过调节下丘脑-垂体-甲状腺轴或通过对骨骼肌的直接影响来影响外周代谢。
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.