Селективные модуляторы рецепторов тиреоидных гормонов

Thyroid hormones have the widest range of control activities, including embryonic development, cell differentiation, metabolism, and cell growth. This diversity of effects is explained by the cellular and tissue context, which is provided by the tissue-specific localization of various types of receptors with different spectrum of activity (nuclear, membrane), and cell-specific set of transcription co-regulators. An excess or deficiency of the thyroid signal in hyper- and hypothyroidism is well studied and successful schemes of therapy have been developed. Along with endocrine, there are a number of somatic diseases, the development of which is accompanied by violation of the thyroid function. First of all, it concerns liver diseases, metabolic syndrome, and type 2 diabetes mellitus (DM2). Therefore, thyroid hormone analogs have therapeutic potential for the normalization of, e.g., lipid metabolism and prevention of chronic liver diseases and heart failure. However, The presence of side effects such as increase in the heart rate, activation of catabolism of muscle tissue, and impaired bone-mineral metabolism in the T3 activity spectrum severely limits the possibility of clinical use of thyromimetics. The separation of hormone functions using selective ligands of individual receptor types is a promising fundamental and practical direction of pharmacology. The present review considers modern notions about molecular mechanisms of the action of thyroid hormones, as well as recent results and future prospects for the search for selective modulators of thyroid hormone receptors.