Laboratory of Endocrinology and Receptor Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
J Clin Endocrinol Metab. 2012 Dec;97(12):4287-92. doi: 10.1210/jc.2012-3080. Epub 2012 Sep 27.
The physiological role of the TSH receptor (TSHR) as a major regulator of thyroid function is well understood, but TSHRs are also expressed in multiple normal extrathyroidal tissues, and the physiological roles of TSHRs in these tissues are unclear. Moreover, TSHRs play a major role in several pathological conditions including hyperthyroidism, hypothyroidism, and thyroid tumors. Small molecule, "drug-like" TSHR agonists, neutral antagonists, and inverse agonists may be useful as probes of TSHR function in extrathyroidal tissues and as leads to develop drugs for several diseases of the thyroid. In this Update, we review the most recent findings regarding the development and use of these small molecule TSHR ligands.
促甲状腺激素受体（TSHR）作为甲状腺功能主要调节剂的生理作用已被充分理解，但 TSHR 也在多种正常甲状腺外组织中表达，其在这些组织中的生理作用尚不清楚。此外，TSHR 在包括甲状腺功能亢进、甲状腺功能减退和甲状腺肿瘤在内的多种病理情况下发挥重要作用。小分子“类药” TSHR 激动剂、中性拮抗剂和反向激动剂可作为研究 TSHR 在甲状腺外组织中功能的探针，并可作为开发几种甲状腺疾病药物的先导化合物。在本综述中，我们回顾了关于这些小分子 TSHR 配体的最新发现及其开发和应用。
