S2RPgrmc1: the cytochrome-related sigma-2 receptor that regulates lipid and drug metabolism and hormone signaling

Multiple laboratories have shown that S2R(Pgrmc1) associates with various P450 proteins and increases cholesterol synthesis via Cyp51. However, the lipogenic role of S2R(Pgrmc1) is tissue-specific. Furthermore, the role of S2R(Pgrmc1) in regulating P450 proteins other than Cyp51 appears to be highly selective, with modest inhibitory activity for Cyp3A4 in vitro and a complex regulatory pattern for Cyp21. Cyp19/aromatase is a therapeutic target in breast cancer, and S2R(Pgrmc1) activated Cyp19 significantly in vitro but modestly in biochemical assays. In summary, S2R(Pgrmc1) is a promising therapeutic target for cancer and possibly cholesterol synthesis but research to date has not identified a major role in P450-mediated drug metabolism.