Columbano Amedeo, Chiellini Grazia, Kowalik Marta Anna
Department of Biomedical Sciences, Unit of Oncology and Molecular Pathology, University of Cagliari, Cagliari, Italy.
Department of Surgical, Medical and Molecular Pathology, University of Pisa, Pisa, Italy.
Gene Expr. 2017 Nov 27;17(4):265-275. doi: 10.3727/105221617X14968563796227. Epub 2017 Jun 13.
Thyroid hormones (THs), namely, 3,5,3'-triiodo-l-thyronine (T3) and 3,5,3',5'-tetraiodo-l-thyronine (thyroxine or T4), influence a variety of physiological processes that have important implications in fetal development, metabolism, cell growth, and proliferation. While THs elicit several beneficial effects on lipid metabolism and improve myocardial contractility, these therapeutically desirable effects are associated to a thyrotoxic state that severely limits the possible use of THs as therapeutic agents. Therefore, several efforts have been made to develop T3 analogs that could retain the beneficial actions (triglyceride, cholesterol, obesity, and body mass lowering) without the adverse TH-dependent side effects. This goal was achieved by the synthesis of TRβ-selective agonists. In this review, we summarize the current knowledge on the effects of one of the best characterized TH analogs, the TRβ1-selective thyromimetic, GC-1. In particular, we review some of the effects of GC-1 on different liver disorders, with reference to its possible clinical application. A brief comment on the possible therapeutic use of GC-1 in extrahepatic disorders is also included.
甲状腺激素(THs),即3,5,3'-三碘-L-甲状腺原氨酸(T3)和3,5,3',5'-四碘-L-甲状腺原氨酸(甲状腺素或T4),影响着多种生理过程,这些过程对胎儿发育、新陈代谢、细胞生长和增殖具有重要意义。虽然甲状腺激素对脂质代谢有多种有益作用,并能改善心肌收缩力,但这些治疗上理想的作用与甲状腺毒症状态相关,这严重限制了甲状腺激素作为治疗药物的可能用途。因此,人们已经做出了多项努力来开发能够保留有益作用(降低甘油三酯、胆固醇、肥胖和体重)而无甲状腺激素依赖性不良副作用的T3类似物。通过合成TRβ选择性激动剂实现了这一目标。在本综述中,我们总结了目前关于特征最明确的甲状腺激素类似物之一——TRβ1选择性拟甲状腺素GC-1作用的知识。特别是,我们参考其可能的临床应用,综述了GC-1对不同肝脏疾病的一些作用。还包括对GC-1在肝外疾病中可能治疗用途的简要评论。