Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Sciences, Shandong University, Qingdao, 266237, China.
Cell Commun Signal. 2020 Sep 9;18(1):146. doi: 10.1186/s12964-020-00620-y.
G protein-coupled receptors (GPCRs) are cell membrane receptors for various ligands. Recent studies have suggested that GPCRs transmit animal steroid hormone signals. Certain GPCRs have been shown to bind steroid hormones, for example, G protein-coupled estrogen receptor 1 (GPER1) binds estrogen in humans, and Drosophila dopamine/ecdysteroid receptor (DopEcR) binds the molting hormone 20-hydroxyecdysone (20E) in insects. This review summarizes the research progress on GPCRs as animal steroid hormone cell membrane receptors, including the nuclear and cell membrane receptors of steroid hormones in mammals and insects, the 20E signaling cascade via GPCRs, termination of 20E signaling, and the relationship between genomic action and the nongenomic action of 20E. Studies indicate that 20E induces a signal via GPCRs to regulate rapid cellular responses, including rapid Ca release from the endoplasmic reticulum and influx from the extracellular medium, as well as rapid protein phosphorylation and subcellular translocation. 20E via the GPCR/Ca/PKC/signaling axis and the GPCR/cAMP/PKA-signaling axis regulates gene transcription by adjusting transcription complex formation and DNA binding activity. GPCRs can bind 20E in the cell membrane and after being isolated, suggesting GPCRs as cell membrane receptors of 20E. This review deepens our understanding of GPCRs as steroid hormone cell membrane receptors and the GPCR-mediated signaling pathway of 20E (20E-GPCR pathway), which will promote further study of steroid hormone signaling via GPCRs, and presents GPCRs as targets to explore new pharmaceutical materials to treat steroid hormone-related diseases or control pest insects. Video abstract.
G 蛋白偶联受体（GPCRs）是各种配体的细胞膜受体。最近的研究表明，GPCR 可传递动物甾体激素信号。某些 GPCR 已被证明可结合甾体激素，例如，G 蛋白偶联雌激素受体 1（GPER1）在人类中结合雌激素，而果蝇多巴胺/蜕皮激素受体（DopEcR）在昆虫中结合蜕皮激素 20-羟化酶（20E）。本文综述了 GPCR 作为动物甾体激素细胞膜受体的研究进展，包括哺乳动物和昆虫甾体激素的核受体和细胞膜受体、GPCR 介导的 20E 信号级联、20E 信号终止以及基因组作用与 20E 的非基因组作用之间的关系。研究表明，20E 通过 GPCR 诱导信号以调节快速的细胞反应，包括内质网中 Ca 的快速释放和细胞外介质的快速内流，以及快速的蛋白质磷酸化和亚细胞转位。20E 通过 GPCR/Ca/PKC/信号轴和 GPCR/cAMP/PKA 信号轴通过调节转录复合物形成和 DNA 结合活性来调节基因转录。GPCR 可在细胞膜上结合 20E 并在分离后结合 20E，提示 GPCR 是 20E 的细胞膜受体。本综述加深了我们对 GPCR 作为甾体激素细胞膜受体和 GPCR 介导的 20E 信号通路（20E-GPCR 通路）的理解，这将促进对 GPCR 介导的甾体激素信号的进一步研究，并将 GPCR 作为探索治疗甾体激素相关疾病或控制害虫的新药物靶点。视频摘要。
