The Effects of Bisphenol-A and its Analogs on Neuronal Oestrogen Sensitive Kinase Pathways.
Bisphenol-A (BPA) is a major endocrine-disrupting chemical, which interferes with several cell signaling pathways. Although studies have suggested that BPA acts as a weak oestrogen agonist at the nuclear oestrogen receptor, ERα, in the brain BPA inhibits anti-oestrogenic effects. This project tested the hypothesis that BPA is a functional agonist/antagonist of the G-protein coupled oestrogen receptor (GPER), via activation of c-Jun-N-terminal kinase (JNK) in neurons. At the same time, I asked whether the widely-used BPA substitutes, Bisphenol-S (BPS) and Bisphenol-F (BPF) might exert effects similar to those of BPA, using the mHippoE-14 (immortalized fetal mouse neuronal) and SH-SY5Y (human female neuroblastoma) cell lines. BPA, BPS and BPF all significantly inhibited GPER – mediated activation of JNK phosphorylation, as well as ERK1/2 phosphorylation. These data suggest that BPA, BPS, and BPF may be the functional antagonists of GPER-mediated oestrogen signaling in the brain.