G protein-coupled estrogen receptor (GPER), or GPR30, specifically binds natural and man-made estrogens.1 It is thought to be involved in estrogen-sensitive cancers.1,2 GPER knockout mice are fertile, although they exhibit thymic atrophy, impaired glucose tolerance, and altered bone growth.1 G-15 is a cell-permeable non-steroidal antagonist of GPER (Ki = 20 nM).3 It displays low affinity cross-reactivity with the classical estrogen receptor (ER), ERα, so that at doses greater than 1 μM it is capable of mediating limited ER-dependent transcriptional activity.4 G-15 antagonizes the anti-depressive effects of estrogen in vivo.3