Perspectives | Correspondence April 2014 | Volume 122 | Issue 4
Crystallographic Analysis and Mimicking of Estradiol Binding: Pedersen et al. Respond
Lars C. Pedersen,1 Linda S. Birnbaum,2 Rajendrakumar A. Gosavi,1 and Gabriel A. Knudsen2
1Laboratory of Structural Biology, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina, USA; 2Laboratory of Toxicology and Toxicokinetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina, USA
Citation: Pedersen LC, Birnbaum LS, Gosavi RA, Knudsen GA. 2014. Crystallographic Analysis and Mimicking of Estradiol Binding: Pedersen et al. Respond. Environ Health Perspect 122:A91–A92; http://dx.doi.org/10.1289/ehp.1307987R
The authors declare that they have no actual or potential competing financial interests.
Published: 1 April 2014
Previous studies have addressed the biological effects of brominated flame retardants (Birnbaum and Staskal 2004; Koike et al. 2013; Mariussen and Fonnum 2003; Ogunbayo et al. 2008), including a 2-year bioassay study performed by the National Toxicology Program (NTP), which demonstrated that tetrabromobisphenol A (TBBPA) can induce aggressive uterine tumors in rats (NTP 2013). As pointed out by Osimitz et al., TBBPA has been shown to bind poorly to the estrogen receptor, providing the impetus to study other pathways such as disruption of steroid transport and metabolism. Other groups have demonstrated the ability of TBBPA and flame retardant metabolites to inhibit estrogen sulfotransferase (SULT1E1), with IC50 (median inhibitory concentration) values near the Km for estradiol (Hamers et al. 2008; Kester et al. 2002; Zhang et al. 1998). Our work (Gosavi et al. 2013) was focused solely on understanding the structural mechanism by which these compounds bind to and inhibit SULT1E1’s ability to metabolize estradiol. The results of our work demonstrate that TBBPA and the 3-OH metabolite of BDE-47, although structurally different, bind in a similar manner at the estradiol binding site. This work suggests that these compounds could have an additive effect on the inhibition of this enzyme. We wholeheartedly agree with Osimitz et al. that the results of our work warrant future studies addressing the potential additive effect of these compounds on steroid metabolism in target tissues.
Birnbaum LS, Staskal DF. 2004. Brominated flame retardants: cause for concern? Environ Health Perspect 112:9–17; doi: 10.1289/ehp.6559.
Gosavi RA, Knudsen GA, Birnbaum LS, Pedersen LC. 2013. Mimicking of estradiol binding by flame retardants and their metabolites: a crystallographic analysis. Environ Health Perspect 121:1194–1199; doi: 10.1289/ehp.1306902.
Hamers T, Kamstra JH, Sonneveld E, Murk AJ, Visser TJ, Van Velzen MJM, et al. 2008. Biotransformation of brominated flame retardants into potentially endocrine-disrupting metabolites, with special attention to 2,2´,4,4´-tetrabromodiphenyl ether (BDE-47). Mol Nutr Food Res 52(2): 284–298.
Kester MHA, Bulduk S, van Toor H, Tibboel D, Meinl W, Glatt H, et al. 2002. Potent inhibition of estrogen sulfotransferase by hydroxylated metabolites of polyhalogenated aromatic hydrocarbons reveals alternative mechanism for estrogenic activity of endocrine disrupters. J Clin Endocr Metab 87(3):1142–1150.
NTP (National Toxicology Program). 2013. Toxicology Studies of Tetrabromobisphenol A in F344/NTac Rats and B6C3F1/N Mice and Toxicology and Carcinogenesis Studies of Tetrabromobisphenol A in Wistar Han [Crl:WI(Han)] Rats and B6CF1/N Mice. TR-587. Available: http://ntp.niehs.nih.gov/NTP/About_NTP/TRPanel/2013/October/DRAFT_TR-587.pdf [accessed 12 March 2014].
Ogunbayo OA, Lai PF, Connolly TJ, Michelangeli F. 2008. Tetrabromobisphenol A (TBBPA), induces cell death in TM4 Sertoli cells by modulating Ca2+ transport proteins and causing dysregulation of Ca2+ homeostasis. Toxicol in Vitro 22:943–952.
EHP is pleased to announce that Prenatal Exposure to Glycol Ethers and Neurocognitive Abilities in 6-Year-Old Children: The PELAGIE Cohort Study, published in EHP on 14 October 2016, has been selected by the Children’s Environmental Health Network (CEHN) as its May 2017 Article of the Month. CEHN Article of the Month summaries discuss the potential policy implications of current children’s environmental health research. The CEHN summary can be viewed here.
Among the Resources now available on our Children’s Health page is the text of Executive Order 13045, “Protection of Children from Environmental Health Risks and Safety Risks” (21 April 1997). The Executive Order noted the particular vulnerabilities of children to environmental hazards, codified the need to identify and alleviate such risks, and created the President’s Task Force on Environmental Health Risks and Safety Risks to Children to identify data resources and promote research in these areas. As we mark 20 years since the order was enacted, we can see how these efforts have produced important research and mitigation of hazards—a strong base for continued work on behalf of children’s environmental health.
EHP is excited to announce that, starting later in May 2017, the journal will transition from a traditional, issue-by-issue publishing model, to a new, article-by-article publishing model known as continuous publication. This is a more modern way of publishing an online journal, and one that should help to significantly improve EHP’s time to publication. (more…)