Exploring novel biomarkers for endocrine disruptor exposure: insights into extra-nuclear signaling pathways of estrogen and androgen receptors

: Synthetic chemicals classified as endocrine disruptors (EDs) pose health risks by interfering with sex-steroid hormone signaling. This study evaluated bisphenol A (BPA) for its effects on ERα, ERβ, and AR expression and extranuclear signaling, including ERα phosphorylation, in human monocytes from healthy male and female donors, and assessed ten additional chemicals in ERα-positive breast cancer cell lines (MCF-7, T47D). BPA increased ERα phosphorylation in both male and female monocytes without altering receptor levels, while modulating downstream signaling in a sex-dependent manner and attenuating DHT- or E2-induced effects. The ten other chemicals similarly enhanced ERα phosphorylation, often independently of direct receptor binding. These findings indicate that ERα phosphorylation is a sensitive, early marker of ED activity across immune and epithelial cells and support its use as a receptor-proximal endpoint to complement conventional transcription-based assays in next-generation ED screening strategies.