Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, University of Campania "L. Vanvitelli", Caserta, Italy.
Department of Sciences and Technologies, University of Sannio, Benevento, Italy.
Endocrine. 2019 Oct;66(1):105-114. doi: 10.1007/s12020-019-02025-5. Epub 2019 Jul 29.
Several metabolic products that derive from L-thyroxine (T4) and 3,3'5-L-triiodothyronine (T3), the main thyroid hormones secreted by the thyroid gland, possess biologic activities. Among these metabolites or derivatives showing physiological actions some have received greater attention: diiodothyronines, iodothyronamines, acetic acid analogues. It is known that increased thyroid hormone (T3 and T4) levels can improve serum lipid profiles and reduce body fat. These positive effects are, however, counterbalanced by adverse effects on the heart, muscle and bone, limiting their use. In addition to the naturally occurring metabolites, thyroid hormone analogues have been developed that either have selective effects on specific tissues or bind selectively to thyroid hormone receptor (TR) isoform. Among these GC-1, KB141, KB2115, and DITPA were deeply investigated and displayed promising therapeutic results in the potential treatment of conditions such as dyslipidemias and obesity. In this review, we summarize the current knowledge of metabolites and analogues of T4 and T3 with reference to their possible clinical application in the treatment of human diseases.
几种代谢产物来源于甲状腺分泌的主要激素 L-甲状腺素 (T4) 和 3,3'5-三碘甲状腺原氨酸 (T3)，具有生物活性。在这些表现出生理作用的代谢产物或衍生物中，有些受到了更多的关注：二碘甲状腺原氨酸、碘甲状腺原氨酸、醋酸类似物。已知增加甲状腺激素 (T3 和 T4) 水平可以改善血清脂质谱并减少体脂肪。然而，这些积极作用被对心脏、肌肉和骨骼的不良影响所抵消，限制了它们的使用。除了天然存在的代谢产物外，还开发了甲状腺激素类似物，它们对特定组织具有选择性作用，或者选择性地与甲状腺激素受体 (TR) 同工型结合。其中，GC-1、KB141、KB2115 和 DITPA 被深入研究，并在治疗血脂异常和肥胖等疾病方面显示出有希望的治疗效果。在这篇综述中，我们总结了 T4 和 T3 的代谢产物和类似物的最新知识，并参考了它们在治疗人类疾病方面的可能临床应用。
