2,3-Bis(4-hydroxyphenyl)-propionitrile (Diarylprepionitrile, DPN) is an ERβ-selective agonist; IC50 = 15nM. DPN protects WT and ARKO mice and significantly decreases IL-1β following LPS treatment in young adult-derived microglia. PPT (Cat. No.H6036, ERa agonist) enhances cell proliferation, while DPN inhibits it. PPT increases Bcl-2 expression, while DPN decreases it. DPN also elevates Bax expression. DPN induces a dose-dependent increase on vitellogenin synthesis. PPT and DPN are effective in dynamically, but differentially regulating intracellular calcium signaling in hippocampal neurons. DPN is more efficacious than PPT in potentiating a physiological concentration of glutamate-induced intracellular Ca2+ rise in these neurons. DPN prevents the development of prostatic hyperplasia and inflammation in testosterone-treated LuRKO mice.