vestnik-bio-msuВестник Московского университета. Серия 16. БиологияVestnik Moskovskogo universiteta. Seriya 16. Biologiya0137-0952Lomonosov Moscow State University, School of Biologyvestnik-bio-msu-932Research ArticleОБЗОРREVIEWНегеномное действие тиреоидных гормонов: роль в регуляции сосудистой системыNongenomic effects of thyroid hormones: role in regulation of the vascular systemhttps://orcid.org/0000-0003-2732-3726СеливановаЕ. К.SelivanovaE. K.

Селиванова Екатерина Константиновна – аспирант, мл. науч. сотр. кафедры физиологии человека и животных биологического факультета МГУ

119234, г. Москва, Ленинские горы, д. 1, стр. 12

Тел.: 8-495-939-14-16

selivanova@mail.bio.msu.ruhttps://orcid.org/0000-0002-4230-3849ТарасоваО. С.TarasovaO. S.

Тарасова Ольга Сергеевна – докт. биол. наук, проф. кафедры физиологии человека и животных биологического факультета МГУ, вед. науч. сотр. лаб. физиологии мышечной деятельности ГНЦ РФ ИМБП РАН

119234, г. Москва, Ленинские горы, д. 1, стр. 12 

123007, г. Москва, Хорошевское ш., 76А

Тел.: 8-495-939-14-16 

 Leninskiye gory 1–12, Moscow, 119234

Khoroshevskoye shosse 76A, Moscow, 123007

ost.msu@gmail.comКафедра физиологии человека и животных, биологический факультет, Московский государственный университет имени М.В. ЛомоносоваРоссияDepartment of Human and Animal Physiology, Faculty of Biology, Lomonosov Moscow State UniversityRussian FederationКафедра физиологии человека и животных, биологический факультет, Московский государственный университет имени М.В. Ломоносова; Лаборатория физиологии мышечной деятельности, Институт медико-биологических проблем, РАНРоссияDepartment of Human and Animal Physiology, Faculty of Biology, Lomonosov Moscow State University; Laboratory of Exercise Physiology, Institute for Biomedical Problems, Russian Academy of SciencesRussian Federation202006112020754226236Copyright © Селиванова Е.К., Тарасова О.С., 20202020Селиванова Е.К., Тарасова О.С.Selivanova E.K., Tarasova O.S.This work is licensed under a Creative Commons Attribution 4.0 License.https://vestnik-bio-msu.elpub.ru/jour/article/view/932

Негеномное действие тиреоидных гормонов (ТГ) проявляется в течение нескольких минут или часов и не зависит от связывания гормона с транскрипционно активными ядерными рецепторами TRα и TRβ. Такое действие характеризуется разнообразием задействованных рецепторов и сигнальных путей, которые могут различаться в разных типах клеток. Тироксин и трийодтиронин способны оказывать негеномное влияние при взаимодействии с транскрипционно неактивными TRα и TRβ в цитоплазме клетки, их укороченными изоформами или интегрином αvβ3. При негеномном действии ТГ также могут изменять транскрипцию генов, но в этом случае их влияние распространяется на более широкий спектр генов, чем при геномном действии. Негеномное действие ТГ часто дополняет геномное, вызывая сходные изменения активности клеток, или же усиливает его, обеспечивая транслокацию TRα и TRβ в ядро или их посттрансляционную модификацию. В сосудистом русле ТГ оказывают негеномное регуляторное влияние на ангиогенез и тонус сосудов (вызывают быструю вазодилатацию). Ключевой сигнальный каскад, опосредующий ангиогенез, включает интегрин αvβ3, протеинкиназу D и деацетилазу гистонов 5. Механизмы быстрой вазодилатации пока изучены недостаточно и могут различаться в разных регионах сосудистого русла. В цитоплазме эндотелиальных клеток негеномное влияние ТГ реализуется с участием рецептора TRα1, фосфоинозитид-3-киназы и NO-синтазы, однако такой механизм не является универсальным. ТГ также могут вызывать вазодилатацию артерий скелетных мышц при взаимодействии с интегрином αvβ3, расположенным в гладкомышечных клетках, однако запускаемые им сигнальные каскады пока не изучены. Знание молекулярных механизмов негеномного влияния ТГ важно для разработки новых способов фармакологической коррекции сосудистых патологий, развитие которых связано с нарушениями тиреоидного статуса.

The nongenomic effects of thyroid hormones develop within minutes or hours and do not depend on the binding of the hormone to the transcriptionally active nuclear receptors TRα and TRβ. These effects are characterized by a variety of receptors and signaling pathways involved, which may be distinct in different cell types. T3 or T4 can induce nongenomic effect by association with transcriptionally inactive TRα and TRβ in the cytoplasm of the cell, their truncated isoforms or integrin αvβ3. With nongenomic action, as well as with genomic action, T3 and T4 can alter gene transcription, but in this case, their influence is extended to wider spectrum of genes. The nongenomic effects of thyroid hormones often complement the genomic ones, causing similar changes in cell activity, or enhance them by providing TRα and TRβ translocation into the nucleus or their post-translational modification. The nongenomic effects of thyroid hormones on the vasculature include angiogenesis and rapid vasodilation. The key signaling cascade mediating angiogenesis includes integrin αvβ3, protein kinase D, and histone deacetylase 5. The mechanisms of rapid vasodilation are still poorly understood and may vary in different regions of the vascular bed. In cytoplasm of endothelial cells, the nongenomic effect of thyroid hormones is mediated by TRα1, PI3K, and NO synthase, but this mechanism is not universal. Thyroid hormones-induced vasodilation of skeletal muscle arteries includes the participation of αvβ3 integrin located in smooth muscle cells, but the signaling cascades triggered by it have not yet been studied. Knowledge of the molecular mechanisms of the nongenomic effect of thyroid hormones is important for the development of new methods of pharmacological correction of vascular pathologies, which are usually associated with thyroid disorders.

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The authors declare that there are no conflicts of interest present.