Aranda Ana, Alonso-Merino Elvira, Zambrano Alberto
Instituto de Investigaciones Biomédicas "Alberto Sols", Consejo Superior de Investigaciones Científicas and Universidad Autónoma de Madrid, Arturo Duperier 4, 28029 Madrid, Spain.
Pediatr Endocrinol Rev. 2013 Sep;11(1):2-13.
The important physiological actions of the thyroid hormones are mediated by binding to nuclear thyroid hormone receptors (TRs), encoded by two genes TRalpha and TRbeta. These receptors act as hormone-dependent transcription factors by binding to DNA motifs located in the regulatory regions of target genes and recruiting coregulators (coactivators and corepresors), which alter chromatin structure. Novel thyromimetics have been developed that bind preferentially TRbeta could be used for treatment of hyperlipidemia and obesity. TRbeta gene mutations cause resistance to thyroid hormones (RTH), characterized by inappropriately high thyroid-stimulating hormone (TSH) levels due to lack of feedback inhibition of thyroid hormones on the hypothalamus and pituitary gland, and to reduced sensitivity of other TRbeta target tissues to thyroid hormones. Very recently, patients heterozygous for TRalpha mutations have been identified. These patients exhibit clinical symptoms of hypothyroidism in TRalpha target tissues such as intestine or hearth and near normal circulating TSH and thyroid hormone levels.
甲状腺激素的重要生理作用是通过与核甲状腺激素受体（TRs）结合来介导的，TRs由TRα和TRβ两个基因编码。这些受体通过与位于靶基因调控区域的DNA基序结合并招募共调节因子（共激活因子和共抑制因子）来充当激素依赖性转录因子，从而改变染色质结构。已开发出优先结合TRβ的新型甲状腺模拟物，可用于治疗高脂血症和肥胖症。TRβ基因突变会导致甲状腺激素抵抗（RTH），其特征是由于甲状腺激素对下丘脑和垂体缺乏反馈抑制，导致促甲状腺激素（TSH）水平异常升高，以及其他TRβ靶组织对甲状腺激素的敏感性降低。最近，已鉴定出TRα突变的杂合子患者。这些患者在肠道或心脏等TRα靶组织中表现出甲状腺功能减退的临床症状，而循环中的TSH和甲状腺激素水平接近正常。
