Correspondence Volume 122 | Issue 4 | April 2014
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 present the abstracts from the 28th annual meeting of the International Society for Environmental Epidemiology (ISEE), held in Rome, Italy, 1–4 September 2016, and hosted by the Department of Epidemiology Lazio Regional Health Service, ASL Roma 1, and the Italian Epidemiological Association. The focus of this year’s conference is current and future challenges in exposure assessment, study design, and data analyses.
For a number of years, EHP has posted accepted manuscripts online as what we termed Advance Publications. The concept here was simple—to get the content online as quickly as possible in an effort both to get authors the attention they deserve and to get readers the information they need. This product has served our community well, but it is not without its flaws. … MORE
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