Direct Evidence Revealing Structural Elements Essential for the High Binding Ability of Bisphenol A to Human Estrogen-Related Receptor-γ

• DOI: 10.1289/ehp.10587
• Publication Date: 2007-10-05T17:03:22Z
• Authors: Hiroyuki Okada; Takatoshi Tokunaga; Xiaohui Liu; Sayaka Takayanagi; Ayami Matsushima; Yasuyuki Shimohig...
• Keywords: Endocrine disruptor; Ligand binding assay; Estrogen receptor alpha

Various lines of evidence have shown that bisphenol A [BPA; HO-C6H4-C(CH3)2-C6H4-OH] acts as an endocrine disruptor when present in very low doses. We recently demonstrated BPA binds strongly to human estrogen-related receptor-gamma (ERR-gamma ) a binding assay using [3H]4-hydroxytamoxifen ([3H]4-OHT). also inhibits the deactivation activity 4-OHT.In study, we intended obtain direct interacts with ERR-gamma strong binder, and clarify structural requirements for its ERR-gamma.We examined [3H]BPA saturation ligand domain analyzed result Scatchard plot analysis. number derivatives were tested competitive tracer luciferase reporter gene assay.[3H]BPA showed KD 5.50 nM at Bmax 14.4 nmol/mg. When evaluate essentials required , found only one two phenol-hydroxyl groups was essential full binding. The maximal attained methyl removed. All potent retained high constitutive basal exhibited distinct inhibitory against 4-OHT.These results indicate phenol are candidates ERR-gamma.