Membrane-associated G protein-coupled dehydroepiandrosterone-sensitive receptor (GPR-DHEA)

The Membrane-associated G protein-coupled dehydroepiandrosterone-sensitive receptor is a cell surface receptor that mediates the rapid, non-genomic effects of the neurosteroid dehydroepiandrosterone (DHEA). Unlike classical steroid receptors that function as nuclear transcription factors, this receptor is localized to the plasma membrane and is coupled to heterotrimeric G proteins, including Gi, Gs, and Gq subtypes. It plays a vital role in neuroprotection by activating pro-survival signaling cascades such as the Src/ERK and PI3K/Akt pathways, which subsequently induce anti-apoptotic proteins like Bcl-2 and Bcl-xL. In the vascular system, the receptor stimulates endothelial nitric oxide synthase (eNOS), promoting vasodilation and maintaining vascular health. Recent research has identified the adhesion GPCR ADGRG2 and the estrogen receptor GPER1 as potential molecular identities for DHEA-sensitive signaling in various tissues, including the reproductive and hepatic systems. Pharmacological modulation of this receptor is a subject of interest for treating neurodegenerative disorders, cardiovascular diseases, and male infertility, although its ability to induce oncogenic microRNAs like miR-21 in certain cancers necessitates careful therapeutic consideration.

Other names

Membrane DHEA receptorG protein-coupled DHEA receptorDHEA-specific membrane binding siteAdhesion G protein-coupled receptor G2 (ADGRG2)G protein-coupled estrogen receptor 1 (GPER1)GPR30GPR64HE6

Activation of heterotrimeric G proteins (primarily Gi, Gs, or Gq subtypes), leading to the rapid activation of intracellular signaling cascades including Src kinase, MAPK/ERK, and PI3K/Akt pathways. This activation results in the induction of anti-apoptotic proteins such as Bcl-2 and Bcl-xL, and the stimulation of endothelial nitric oxide synthase (eNOS) for vascular regulation.