РЕЦЕПТОР ТИРЕОТРОПНОГО ГОРМОНА: РОЛЬ В РАЗВИТИИ ТИРЕОИДНОЙ ПАТОЛОГИИ И ПЕРСПЕКТИВНАЯ МИШЕНЬ ДЛЯ ЕЕ КОРРЕКЦИИ
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Ключевые слова

рецептор тиреотропина
тиреотропный гормон
аллостерический регулятор
щитовидная железа
трансмембранный домен
тиреоидный гормон
аутоиммунный гипертиреоз

Как цитировать

Фокина, Е. А., & Шпаков, А. О. (2022). РЕЦЕПТОР ТИРЕОТРОПНОГО ГОРМОНА: РОЛЬ В РАЗВИТИИ ТИРЕОИДНОЙ ПАТОЛОГИИ И ПЕРСПЕКТИВНАЯ МИШЕНЬ ДЛЯ ЕЕ КОРРЕКЦИИ. Российский физиологический журнал им. И. М. Сеченова, 108(9), 1094–1113. https://doi.org/10.31857/S0869813922090060

Аннотация

Одним из ключевых компонентов, ответственных за ответ щитовидной железы на стимуляцию тиреотропным гормоном (ТТГ), является рецептор ТТГ, относящийся к суперсемейству G-белок-сопряженных рецепторов. Связывание ТТГ или стимулирующих аутоантител с внеклеточным доменом рецептора ТТГ приводит к запуску множества сигнальных путей в клетках-мишенях, которые реализуются через различные типы G-белков и β-аррестины. Ингибирующие аутоантитела, напротив, подавляют активность рецептора ТТГ, индуцируя гипотиреоидные состояния. Активирующие мутации приводят к конститутивно активным формам рецептора ТТГ и могут стать триггером онкологических заболеваний. В соответствии с этим, рецептор ТТГ является одной из ключевых мишеней для регуляции функций щитовидной железы и тиреоидного статуса, а также для коррекции заболеваний, обусловленных изменением активности рецептора ТТГ (аутоиммунные гипертиреоз и гипотиреоз, офтальмопатия Грейвса, тиреоидный рак). Препараты ТТГ исключительно редко применяются в медицине, что обусловлено их иммуногенностью и серьезными побочными эффектами. Наибольшие перспективы связывают с разработкой низкомолекулярных аллостерических регуляторов рецептора ТТГ с активностью полных и инверсионных агонистов и нейтральных антагонистов. Они способны проникать в аллостерический сайт, расположенный в трансмембранном домене рецептора ТТГ, и специфично связываться с ним, контролируя, тем самым, способность рецептора взаимодействовать с G-белками и β-аррестинами. Аллостерические регуляторы не влияют на связывание ТТГ и аутоантител с рецептором, что создает возможности для мягкой и селективной регуляции функций щитовидной железы без критических изменений уровня ТТГ и тиреоидных гормонов. Современному состоянию проблемы регуляции активности рецептора ТТГ, в том числе с помощью лигандов его аллостерических сайтов, посвящен настоящий обзор.

https://doi.org/10.31857/S0869813922090060
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