GPER1,即G蛋白偶联雌激素受体1,是一种非经典的雌激素受体,与传统的核雌激素受体α(ERα)和β(ERβ)不同,GPER1定位于细胞膜上,并介导雌激素的快速非基因组效应。GPER1通过结合雌激素或合成激动剂,如G-1,激活细胞内的信号级联反应,影响基因表达和细胞功能。GPER1在多种组织中均有表达,包括甲状腺、乳腺、大脑和骨骼等,其在维持细胞生理功能和病理过程中的作用日益受到关注[1,2,3,4,5,6,7,8]。
雌激素通过直接或间接的方式调节基因表达。传统的雌激素受体α和β通过结合雌激素后形成二聚体,进而与DNA上的雌激素反应元件结合,激活或抑制基因转录。而GPER1则通过G蛋白信号途径,激活多种蛋白激酶级联反应,如cAMP/PKA、PLC/PKC和ERK/MAPK等,从而影响基因表达和细胞功能[1,2]。此外,雌激素信号通路还与表观遗传机制密切相关,如组蛋白修饰、microRNA和DNA甲基化等,共同调节基因表达和细胞功能[2,5]。
GPER1在多种疾病的发生和发展中发挥重要作用。例如,在甲状腺癌中,GPER1的表达水平降低,且与患者的临床特征相关,如淋巴结转移、女性性别和BRAF突变等[3]。此外,GPER1的表达水平与甲状腺分化基因的表达水平呈正相关,提示GPER1在甲状腺癌的发生发展中可能发挥重要作用[3]。在乳腺肿瘤中,GPER1的表达水平与肿瘤的增殖、迁移、凋亡和转移等过程密切相关,提示GPER1可能成为乳腺肿瘤治疗的新靶点[10]。此外,GPER1在骨骼、大脑等组织中的表达和功能也受到关注,如GPER1在维持骨再生、调节海马突触可塑性和认知功能等方面发挥重要作用[4,8,9]。
综上所述,GPER1是一种重要的非经典雌激素受体,通过G蛋白信号途径介导雌激素的快速非基因组效应,影响基因表达和细胞功能。GPER1在多种疾病的发生和发展中发挥重要作用,如甲状腺癌、乳腺肿瘤等,且与骨再生、海马突触可塑性和认知功能等生理过程密切相关。深入研究GPER1的生物学功能和作用机制,有助于揭示雌激素信号通路的复杂性和多样性,为相关疾病的治疗和预防提供新的思路和策略。
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