Endocrine disruption via estrogen receptors that participate in nongenomic signaling pathways

► Compounds that have estrogenic effects can act via either genomic or nongenomic pathways. ► ERs α and β act from either the nucleus or the cell membrane; GPER acts at membranes. ► Estrogens acting on these signaling systems include a variety of physiologic metabolites, food-based estrogens, environmental contaminant estrogens, and pharmaceutical estrogens. ► Nongenomic estrogenic signaling responses often oscillate with time, and have non-monotonic concentration responses. ► Nongenomic estrogenic endpoints can be reached very rapidly, or can build up over time and be sustained.