Endocrine Abstracts

Introduction: There are concerns about the combined estrogenic effects of endocrine disrupting chemicals (EDCs), since mixtures of these chemicals exist in our environment. This study investigated potential synergistic interactions between bisphenol A (BPA) and isobutylparaben (IBP), which are major xenoestrogens used in the manufacture of plastics, cosmetics, drugs, and other products. The combined effects of these two chemicals were analyzed by measuring expression of calbindin-D9k (CaBP-9k) in the rat pituitary GH3 cells.

Methods: GH3 cells were treated with single and combination doses of both chemicals (BPA single doses: 10⁻⁷, 10⁻⁶ and 10⁻⁵ M; IBP single doses: 10⁻⁷, 10⁻⁶ and 10⁻⁵ M, and each of BPA and IBP doses combined). Prior to treatment, the cells were temporarily transfected with a plasmid containing an estrogen response element (ERE). A luciferase activity was measured as an indicator of ERE activation by 17β-estradiol (E2), BPA, and IBP.

Results: In addition to E2, EDC induced a significant increase in luciferase activity. Twenty-four hours after treatment, dose-dependent effects were observed in both single and combined groups, and several combined doses induced a synergistic increase in the expression of CaBP-9k and progesterone receptor (PR) at both transcriptional and translational levels. Pre-treatment with fulvestrant, a pure estrogen antagonist, significantly reversed EDC-induced CaBP-9k and PR upregulation in GH3 cells.

Conclusions: Our results indicate that BPA and IBP may have synergistically increased estrogenic potency via an estrogen receptor-mediated pathway.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.