DHEA-specific receptor

The DHEA-specific receptor is a putative G protein-coupled receptor (GPCR) located on the plasma membrane of various cell types, most notably vascular endothelial cells and smooth muscle cells. Unlike the classical nuclear androgen and estrogen receptors, this receptor mediates rapid, non-genomic effects of dehydroepiandrosterone (DHEA), such as the activation of endothelial nitric oxide synthase (eNOS) and the mitogen-activated protein kinase (MAPK) pathway. Activation of the receptor by DHEA promotes nitric oxide production, leading to vasodilation and improved endothelial function, which has significant implications for cardiovascular health and the treatment of conditions like atherosclerosis and erectile dysfunction. While its exact molecular identity has been a subject of debate, candidates such as GPR174 and the neurotrophin receptor TrkA have been proposed as potential mediators of DHEA's specific actions. The receptor is considered a therapeutic target for its potential to harness the beneficial effects of DHEA without the systemic hormonal side effects associated with its conversion into potent androgens or estrogens. Research into this receptor aims to develop selective agonists that can provide neuroprotective and cardioprotective benefits while minimizing off-target hormonal activity.

Other names

Membrane-bound dehydroepiandrosterone receptorPutative DHEA receptormDBSMembrane DHEA binding site

Agonism