Роль кортикотропин-рилизинг гормона и его рецепторов в регуляции нейрофизиологических и поведенческих реакций на стресс

Стресс является неотъемлемой частью повседневной жизни. Нейропептид кортикотропинрилизинг гормон (CRH, также называемый CRF и кортиколиберином) играет ключевую роль в интеграции нейроэндокринных, вегетативных и поведенческих реакций на стресс. Активация гипоталамо-гипофизарной-надпочечниковой системы нейронами паравентрикулярного ядра гипоталамуса (PVN), основного места синтеза CRH, запускает стрессорную реакцию. Помимо гипоталамуса, CRH широко распространен во внегипоталамических структурах головного мозга, где он функционирует как нейромодулятор для координации и взаимодействия между гуморальными и поведенческими аспектами реакции на стресс. Аксоны нейронов, экспрессирующих CRH, направляются к различным структурам головного мозга, где нейропептид взаимодействует со специфическими рецепторами (CRHR1, CRHR2) и может оказывать влияние на различные медиаторные системы, которые действуют сообща для передачи сигналов в разные области мозга, чтобы вызвать множество реакций на стресс. При этом воздействие стресса на функции мозга варьирует от поведенческой адаптации до повышения выживаемости и увеличения риска развития психических расстройств. Нарушения в регуляции системы CRH непосредственно связаны со следующими расстройствами: психическими патологиями (депрессией, тревожностью, зависимостями), отклонениями нейроэндокринологических функций, воспалением, а также с возникновением и развитием нейродегенеративных заболеваний, таких как болезнь Альцгеймера. Кроме того, установлена роль CRH как регулятора структуры нейронов в областях развивающегося и зрелого мозга. На данный момент проведены исследования, в которых CRHR1 выступает мишенью для антидепрессантов, в качестве которых используются антагонисты этого рецептора. В связи с этим исследование участия системы CRH и его рецепторов в негативных эффектах на гормон-зависимые системы, а также возможности их предотвращения является перспективной задачей современной физиологической генетики. В настоящем обзоре внимание уделено роли CRH в регуляции реакции на стресс, а также участию внегипоталамического CRH в патофизиологии и коррекции психических расстройств.

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