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Влияние высокоаффинного СТГ-связывающего белка на результаты оценки уровня СТГ в сыворотке крови



Высокоаффинный СТГ-связывающий белок может препятствовать проведению иммуиоанализа СТГ в сыворотке крови из-за конкуренции с антителами за связывание с СТГ. Как правило, антитела, особенно поликлональные, обладают более высоким сродством к СТГ, чем GHBP. Тем не менее, в зависимости от условий проведения анализа величина ошибки, обусловленной присутствием в анализируемых образцах GHBP, может оказаться достаточно большой. К числу особенно подверженных такой ошибке методик можно отнести те, в которых используются моноклональные антитела против СТГ, которые обладают сравнительно низкой аффинностью, методы экспресс-анализа с ограниченным временем инкубации в неравновесных условиях, а также малочувствительные методики, где используются значительные объемы сыворотки крови. Проведение количественного анализа в неравнозначных условиях представляется довольно проблематичным, поскольку для перехода СТГ из комплекса СТГ—GHBP в комплекс с антителом требуется определенное время. По данным различных исследований, величина ошибки при определении СТГ, обусловленных присутствием СТГ-связывающего белка, может варьировать от несущественной до весьма заметной (Jan et ql., 1991; Chapman et al., 1994; Jansson et al., 1997; Fisker et al., 1998). Очень важно оценивать степень ошибки, вносимой присутствием GHBP, в случае каждой отдельной методики определения СТГ, поскольку все факторы, которые могут влиять на величину этой ошибки, неизвестны. Кроме того, протоколы проведения оценки должны быть оптимизированы, с тем чтобы сделать такую ошибку минимальной.

Заключение

В крови и других биологических жидкостях обнаружены два СТГ-связывающих белка (GHBP). Высокоаффинный GHBP представляет собой эктокомпонент рецептора соматотропного гормона, который образуется либо в результате специфического протеолитического расщепления мембранных рецепторов СТГ ферментом ТАСЕ — представителем (ADAM-17) семейства металлопротеииаз ADAM, либо секретируется в виде самостоятельного продукта мРНК, образующейся в результате альтернативного синтеза. Расщепление с участием ТАСЕ происходит в участке белка, расположенном в непосредственной близости к мембране. GHBP оказывает комплексное воздействие на транспорт СТГ в кровеносной системе, клиренс и проявление физиологического эффекта гормона роста, усиливая и ослабляя его воздействие в различных ситуациях. Физиологическое значение СТГ-связывающего гормона в регуляторной системе соматотропного гормона еще окончательно не раскрыто. Уровень GHBP в крови, по-видимому, отражает чувствительность организма к соматотропному гормону, это предположительно обусловлено количественной взаимозависимостью GHBP и рецептора СТГ. Механизмы регуляции уровня СТГ-связывающего белка в сыворотке достаточно сложны и варьируют у разных видов, в числе основных определяющих факторов — процессы онтогенеза и развития, характер питания, пол/уровень эстрогенов, у грызунов — состояние беременности. В диагностике применение СТГ-связывающих белков сегодня ограничивается обнаружением синдрома Ларона — генетически обусловленного заболевания, вызванного нечувствительностью организма к СТГ. Присутствие GHBP может вносить ошибку при количественном определении соматотропного гормона, что требует дальнейшей оптимизации методов анализа СТГ.

Низкоаффинный СТГ-связывающий белок представляет собой трансформированный а2-макроглобулин, который, очевидно, играет незначительную роль в биологии соматотропного гормона.

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