UDC

577.175.44

DOI

10.37482/2687-1491-Z234

Authors

Yuliya A. Shatyr* ORCID: https://orcid.org/0000-0001-9279-5282
Galina A. Sroslova** ORCID: https://orcid.org/0000-0002-9118-7098
Nikita O. Nazarov*** ORCID: https://orcid.org/0000-0002-3997-0886
***Centre for the Introduction of Changes of the Ministry of Health

Abstract

Thyroid hormones (THs) are involved in a number of physiological processes occurring in a living organism. They participate in the regulation of the nervous, respiratory, cardiovascular, muscular, and osteoarticular systems, as well as in the processes of thermogenesis, sleep and wakefulness, and reproductive function, and modulate a number of neurotransmitter systems in the brain. Studying the mechanism of TH action in the body is necessary both to understand the reactions these hormones are involved in and to develop ways to regulate their activity. Based on the results of the analysis of Russian and foreign studies for 2011–2023, in line with the current ideas about the regulation of activity and cellular-level mechanism of action of THs, the review points out the specific features and principles of cellular regulation of THs, describes the processes of TH activation under the action of deiodinase enzymes, and characterizes the biological effect of TH regulation. In addition, the mechanisms of genomic and non-genomic action of THs are presented. It has been shown that the genomic (“classical”) action of THs through modulation of the transcription of specific genes affects the growth, development, differentiation and maintenance of the normal functioning of target tissues. Non-genomic mechanisms of TH action are mediated by the plasma membrane or cytoplasmic receptors and regulate the processes of growth, development and metabolism in the body. At the same time, the non-genomic action of THs can both be realized independently of the genomic action and complement, enhance or inhibit the effects of TH binding to transcriptionally active nuclear receptors during the implementation of TH genomic action. According to the results of the study, TH action at the genomic and non-genomic levels is realized in a complex manner, and it is the interaction between the genomic and non-genomic influence of THs that determines the effectiveness of thyroid regulation of cellular processes.

Keywords

thyroid hormones, thyroid gland, triiodothyronine, thyroxine, deiodinases, genomic action, non-genomic action

References

1. Davtyan A.R., Pamaev S.V., Davudov I.T. Issledovatel’skaya aktivnost’ u samok myshey linii C3H-A na fone izmenennogo tireoidnogo statusa [The Influence of Experimentally Changed Thyroid Status on Cognitivity of Female Inbred Mice C3H-A]. Smolenskiy meditsinskiy al’manakh, 2019, no. 1, pp. 87–89.
2. Kazakou P., Nicolaides N.C., Chrousos G.P. Basic Concepts and Hormonal Regulators of the Stress System. Horm. Res. Paediatr., 2023, vol. 96, no. 1, pp. 8–16. https://doi.org/10.1159/000523975
3. Litwack G. Chapter 5 – Thyroid Hormones. Litwack G. Hormones. London, 2022, pp. 101–121. https://doi.org/10.1016/B978-0-323-90262-5.00028-7
4. Luongo C., Dentice M., Salvatore D. Deiodinases and Their Intricate Role in Thyroid Hormone Homeostasis. Nat. Rev. Endocrinol., 2019, vol. 15, pp. 479–488. https://doi.org/10.1038/s41574-019-0218-2
5. Tedeschi L., Vassalle C., Iervasi G., Sabatino L. Main Factors Involved in Thyroid Hormone Action. Molecules, 2021, vol. 26, no. 23. Art. no. 7337. https://doi.org/10.3390/molecules26237337
6. Lasa M., Contreras-Jurado C. Thyroid Hormones Act as Modulators of Inflammation Through Their Nuclear Receptors. Front. Endocrinol., 2022, vol. 13. Art. no. 937099. https://doi.org/10.3389/fendo.2022.937099
7. Cioffi F., Giacco A., Goglia F., Silvestri E. Bioenergetic Aspects of Mitochondrial Actions of Thyroid Hormones. Cells, 2022, vol. 11, no. 6. Art. no. 997. https://doi.org/10.3390/cells11060997
8. Russo S.C., Salas-Lucia F., Bianco A.C. Deiodinases and the Metabolic Code for Thyroid Hormone Action. Endocrinology, 2021, vol. 162, no. 8. Art. no. bqab059. https://doi.org/10.1210/endocr/bqab059
9. Forrest D., Hernandez A. ABCD of Thyroid Hormone Action: After and Before Cloning of Deiodinase Genes. Endocrinology, 2021, vol. 162, no. 10. Art. no. bqab151. https://doi.org/10.1210/endocr/bqab151
10. Bianco A.C., Dumitrescu A., Gereben B., Ribeiro M.O., Fonseca T.L., Fernandes G.W., Bocco B.M.L.C. Paradigms of Dynamic Control of Thyroid Hormone Signaling. Endocr. Rev., 2019, vol. 40, no. 4, pp. 1000–1047. https://doi.org/10.1210/er.2018-00275
11. Al-Suhaimi E.A., Khan F.A. Thyroid Glands: Physiology and Structure. Al-Suhaimi E.A. (ed.). Emerging Concepts in Endocrine Structure and Functions. Singapore, 2022, pp. 133–160. https://doi.org/10.1007/978-981-16-9016-7_5
12. Mullur R., Liu Y.-Y., Brent G.A. Thyroid Hormone Regulation of Metabolism. Physiol. Rev., 2014, vol. 94, no. 2, pp. 355–382. https://doi.org/10.1152/physrev.00030.2013
13. McDermott M.T. Hypothyroidism. Ann. Intern. Med., 2020, vol. 173, no. 1, pp. ITC1–ITC16. https://doi.org/10.7326/AITC202007070
14. Glushakov R.I., Proshin S.N., Tapil’skaya N.I. Rol’ tireoidnykh gormonov v regulyatsii angiogeneza, kletochnoy proliferatsii i migratsii [The Role of Thyroid Hormones in the Regulation of the Angiogenesis and Cells Proliferations]. Geny i kletki, 2011, vol. 6, no. 4, pp. 26–33.
15. Machado M., Bachini F., Itaborahy A. Thyroid Hormones and Skeletal Muscle Beyond Thermogenesis. J. Sci. Sport Exerc., 2023, vol. 6, pp. 315–323. https://doi.org/10.1007/s42978-023-00235-y
16. Ma Z., Song P., Ji D., Zheng M., Qiu Z., Liu Z., Wang B. Thyroid Hormones as Biomarkers of Lung Cancer: A Retrospective Study. Ann. Med., 2023, vol. 55, no. 1. https://doi.org/10.1080/07853890.2023.2196088
17. Visser W.E., Friesema E.C.H., Visser T.J. Minireview: Thyroid Hormone Transporters: The Knowns and the Unknowns. Mol. Endocrinol., 2011, vol. 25, no. 1, pp. 1–14. https://doi.org/10.1210/me.2010-0095
18. Sharlin D.S., Visser T.J., Forrest D. Developmental and Cell-Specific Expression of Thyroid Hormone Transporters in the Mouse Cochlea. Endocrinology, 2011, vol. 152, no. 12, pp. 5053–5064. https://doi.org/10.1210/en.2011-1372
19. Bernal J. Thyroid Hormone Transport in Developing Brain. Curr. Opin. Endocrinol. Diabetes Obes., 2011, vol. 18, no. 5, pp. 295–299. https://doi.org/10.1097/MED.0b013e32834a78b3
20. Giammanco M., Di Liegro C.M., Schiera G., Di Liegro I. Genomic and Non-Genomic Mechanisms of Action of Thyroid Hormones and Their Catabolite 3,5-Diiodo-L-Thyronine in Mammals. Int. J. Mol. Sci., 2020, vol. 21, no. 11. Art. no. 4140. https://doi.org/10.3390/ijms21114140
21. Davis P.J., Leonard J.L., Lin H.Y., Leinung M., Mousa S.A. Molecular Basis of Nongenomic Actions of Thyroid Hormone. Vitam. Horm., 2018, vol. 106, pp. 67–96. https://doi.org/10.1016/bs.vh.2017.06.001
22. Incerpi S., Gionfra F., De Luca R., Candelotti E., De Vito P., Percario Z.A., Leone S., Gnocchi D., Rossi M., Caruso F., Scapin S., Davis P.J., Lin H.Y., Affabris E., Pedersen J.Z. Extranuclear Effects of Thyroid Hormones and Analogs During Development: An Old Mechanism with Emerging Roles. Front. Endocrinol. (Lausanne), 2022, vol. 13. Art. no. 961744. https://doi.org/10.3389/fendo.2022.961744
23. Almojali A.I., Almalki S.A., Alothman A.S., Masuadi E.M., Alaqeel M.K. The Prevalence and Association of Stress with Sleep Quality Among Medical Students. J. Epidemiol. Glob. Health, 2017, vol. 7, no. 3, pp. 169–174. https://doi.org/10.1016/j.jegh.2017.04.005
24. Markevich T.N., Gorodetskaya I.V. Vliyanie stressa na uroven’ yodsoderzhashchikh gormonov shchitovidnoy zhelezy [The Influence of Stress on the Level of Iodine-Containing Thyroid Hormones]. Dostizheniya fundamental’noy, klinicheskoy meditsiny i farmatsii [Achievements of Fundamental, Clinical Medicine and Pharmacy]. Vitebsk, 2021, pp. 282–284.
25. Zyabisheva V.N. Relevance of Physiological Research in the European North of Russia Exemplified by Studies on the Photoperiodic Dynamics of Thyroid Profile Parameters. J. Med. Biol. Res., 2022, vol. 10, no. 2, pp. 180–183. https://doi.org/10.37482/2687-1491-Z100
26. Selivanova E.K., Tarasova O.S. Negenomnoe deystvie tireoidnykh gormonov: rol’ v regulyatsii sosudistoy sistemy [Nongenomic Effects of Thyroid Hormones: Role in Regulation of the Vascular System]. Vestnik Moskovskogo universiteta. Ser. 16: Biologiya, 2020, vol. 75, no. 4, pp. 226–236.
27. Nappi A., Murolo M., Sagliocchi S., Miro C., Cicatiello A.G., Di Cicco E., Di Paola R., Raia M., D’Esposito L., Stornaiuolo M., Dentice M. Selective Inhibition of Genomic and Non-Genomic Effects of Thyroid Hormone Regulates Muscle Cell Differentiation and Metabolic Behavior. Int. J. Mol. Sci., 2021, vol. 22, no. 13. Art. no. 7175. https://doi.org/10.3390/ijms22137175
28. Liu Y.-C., Yeh C.-T., Lin K.-H. Molecular Functions of Thyroid Hormone Signaling in Regulation of Cancer Progression and Anti-Apoptosis. Int. J. Mol. Sci., 2019, vol. 20, no. 20. Art. no. 4986. https://doi.org/10.3390/ijms20204986
29. Lanni A., Moreno M., Goglia F. Mitochondrial Actions of Thyroid Hormone. Compr. Physiol., 2016, vol. 6, no. 4, pp. 1591–1607. https://doi.org/10.1002/cphy.c150019