G protein-coupled receptors function as cell membrane receptors for the steroid hormone 20-hydroxyecdysone

Abstract

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 Ca2+ release from the endoplasmic reticulum and influx from the extracellular medium, as well as rapid protein phosphorylation and subcellular translocation. 20E via the GPCR/Ca2+/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. Graphical abstract

MiR‐3017b contributes to metamorphosis by targeting sarco/endoplasmic reticulum Ca2+ATPase in Tribolium castaneum

“…High steroids titre pulses can rapidly induce Ca 2+ levels through ErGPCRs in cytomembrane by affecting both influx and intracellular Ca 2+ stores. The increased Ca 2+ triggers 20E‐response gene transcription and apoptosis by mediating the formation of EcRB1/USP1 transcriptional complexes and binding to the promoter for 20E pathway downstream gene (Cai et al 2014; Jing et al, 2015; Zhao, 2020). As a Calcium ion pump, SERCA transports intracellular free Ca 2+ into the ER, which is one of the critical factors for maintaining the homeostasis of intracellular Ca 2+ ions (Clapham, 2007; Lipskaia et al, 2009).…”

Identification and Functional Analysis of G Protein-Coupled Receptors in 20-Hydroxyecdysone Signaling From the Helicoverpa armigera Genome

“…The differences among the GPCRs in 20E signaling have been explained by their induced downstream effects, including ErGPCR-1 inducing the Ca 2+ -PKC signaling, while ErGPCR-2 inducing the GPCR-cAMP-PKA and GPCR-Ca 2+ -PKC signaling, increasing 20E entry, and being internalized by 20E induction. DopEcR of H. armigera directly interacts with Gαs and Gαq under the induction of 20E to increase the levels of cAMP and Ca 2+ ( Zhao, 2020 ). ErGPCR-3 has very similar characteristics to ErGPCR-2 ( Kang et al, 2021 ).…”

“…The dopamine/ecdysteroid receptor (DopEcR) transmits the non-genomic signal of insect molting hormone 20-hydroxyecdysone (20E) in Drosophila ( Srivastava et al, 2005 ) and in Helicoverpa armigera ( Kang et al, 2019 ). To date, several GPCRs have been proven to transmit 20E signals in H. armigera ( Zhao, 2020 ), including ecdysone-responsible GPCR 1 (ErGPCR-1), ecdysone-responsible GPCR 2 (ErGPCR-2), and ecdysone-responsible GPCR 3 (ErGPCR-3) ( Cai et al, 2014a ; Wang et al, 2015 ; Kang et al, 2021 ). These data suggest that several GPCRs function as steroid hormone receptors; however, whether any other GPCRs transmit 20E signals, and the mechanism by which several GPCRs function in 20E signaling, are unclear.…”

Ecdysis Triggering Hormone, Eclosion Hormone, and Crustacean Cardioactive Peptide Play Essential but Different Roles in the Molting Process of Mud Crab, Scylla paramamosain

“…Therefore, an increase of ecdysteroid titer in the hemolymph is needed for the start of the molting process. A series of ecdysis-related genes are expressed under the influence of cyclical fluctuations of ecdysone, followed by the binding with nuclear receptors to transmit ecdysis signals, so that the crustaceans complete the pre-molting preparations on time and accurately (Zhao, 2020). When molting begin, the initiation of molting behavior occurs (Song et al, 2017).…”