GPCR-mediated rapid, non-genomic actions of steroids: Comparisons between DmDopEcR and GPER1 (GPR30)

- Some of the rapid non-genomic actions of steroids can be mediated by GPCRs.
- DmDopEcR is a Drosophila GPCR activated by ecdysone and dopamine.
- GPER1 is activated by 17β-estradiol, and perhaps by aldosterone and catecholamines.
- DmDopEcR and GPER1 appear to share a number of similar properties.
- The receptors share similar cellular locations and some pharmacological properties.

Steroid hormones classically mediate their actions by binding to intracellular receptor proteins that migrate to the nucleus and act as transcription factors to change gene expression. However, evidence is now accumulating for rapid, non-genomic effects of steroids. There is considerable controversy over the mechanisms underlying such effects. In a number of cases evidence has been presented for the direct activation of G-protein coupled receptors (GPCRs) by steroids, either at the plasma membrane, or at intracellular locations. Here, we will focus on the non-genomic actions of ecdysteroids on a Drosophila GPCR, DopEcR (CG18314), which can be activated by both ecdysone and the catecholamine, dopamine. We will also point out parallels between this system and the activation of the vertebrate GPCR, GPER1 (GPR30), which is thought to be activated by 17β-estradiol. We propose that the cellular localization and signalling properties of both DopEcR and GPER1 may be cell specific and depend upon their interactions with both accessory molecules and signalling pathways.