БИОХИМИЯ, 2026, том 91, вып. 5, с. 770–796

УДК 577.17

Гипоталамическая регуляция гонадной оси и влияние на нее лептина и инсулина

Обзор

© 2026 И.И. Зорина *zorina.inna.spb@gmail.com, К.В. Деркач, А.О. Шпаков

ФГБУН Институт эволюционной физиологии и биохимии имени И.М. Сеченова РАН (ИЭФБ РАН), 194223 Санкт-Петербург, Россия

Поступила в редакцию 11.02.2026
После доработки 08.04.2026
Принята к публикации 08.04.2026

DOI: 10.7868/S3034529426050052

КЛЮЧЕВЫЕ СЛОВА: лептин, инсулин, гипоталамус, гонадная ось, кисспептин, меланокортин, агути-подобный пептид, нейропептид Y, инсулиновая система, лептиновый сигналинг, репродукция, фертильность, пищевое поведение.

Аннотация

Гипоталамо-гипофизарно-гонадная (ГГГ, гонадная) ось отвечает за регуляцию репродуктивных функций, а ее активность регулируется множеством гормонов, включая лептин и инсулин. Их ключевой мишенью являются гипоталамические нейроны, экспрессирующие гонадолиберин (GnRH), регулирующий секрецию гонадотропинов и контролирующий тем самым половое созревание и фертильность. Основной функцией лептина и инсулина в гипоталамусе является осуществление функциональной взаимосвязи между доступностью энергетических ресурсов и их расходом, с одной стороны, и репродукцией, определяемой в том числе активностью GnRH-нейронов, с другой. Воздействие лептина и инсулина на GnRH-нейроны, как правило, носит опосредованный характер и реализуется через другие гипоталамические нейроны, что обеспечивает более тонкую, многоуровневую регуляцию их активности. Мишенями лептина и инсулина являются различные типы экспрессирующих кисспептин (Kiss1) нейронов, а также нейроны, экспрессирующие проопиомеланокортин (POMC), прекурсор анорексигенных меланокортиновых пептидов, и орексигенные факторы – агути-подобный пептид (AgRP) и нейропептид Y (NPY). Через Kiss1‑ и POMC‑нейроны осуществляется позитивная регуляция GnRH-нейронов, в то время как AgRP/NPY-нейроны вовлечены преимущественно в их негативную регуляцию. Выраженность эффектов лептина и инсулина на Kiss1‑, POMC‑ и AgRP/NPY‑нейроны и в конечном счете на GnRH‑нейроны и ГГГ‑ось в целом зависит от физиологического состояния организма, включая его метаболический статус, стадию полового созревания, пол. Эти эффекты подвержены значительным изменениям при ожирении и сахарном диабете 2‑го типа, внося существенный вклад в этиологию и патогенез ассоциированных с ними репродуктивных расстройств. Настоящий обзор посвящен рассмотрению современного состояния проблемы инсулиновой и лептиновой регуляции гипоталамического звена ГГГ‑оси в норме и при патологии, а также нерешенным проблемам в этой области. Расшифровка молекулярных основ такой регуляции открывает широкие перспективы для разработки новых фармакологических подходов, направленных на восстановление репродуктивных функций при ожирении и диабетической патологии.

Сноски

* Адресат для корреспонденции.

Вклад авторов

З.И.И., Д.К.В., Ш.А.О. – написание и редактирование текста статьи; З.И.И., Д.К.В. – подготовка иллюстраций; Ш.А.О. – концепция и руководство работой.

Финансирование

Работа выполнена на средства государственного бюджета Минобрнауки России по государственному заданию № 075-00264-26-00 (ИЭФБ РАН).

Благодарности

Авторы выражают благодарность А.И. Зориной за помощь в подготовке иллюстраций.

Конфликт интересов

Авторы заявляют об отсутствии конфликта интересов.

Соблюдение этических норм

Настоящая статья не содержит описания каких-либо исследований с участием людей или животных в качестве объектов.

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