skip to main content
DOE PAGES title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Comparative estrogenicity of endogenous, environmental and dietary estrogens in pregnant women II: Total estrogenicity calculations accounting for competitive protein and receptor binding and potency

Abstract

Evaluating the biological significance of human-relevant exposures to environmental estrogens involves assessing the individual and total estrogenicity of endogenous and exogenous estrogens found in serum, for example from biomonitoring studies. We developed a method for this assessment by integrating approaches for (i) measuring total hormone concentrations by mass spectrometry (Fleck et al., 2017), (ii) calculating hormone bioavailable concentrations in serum and, (iii) solving multiple equilibria between estrogenic ligands and receptors, and (iv) quantitatively describing key elements of estrogen potency. The approach was applied to endogenous (E1, E2,E3, E4), environmental (BPA), and dietary Genistein (GEN), Daidzein (DDZ) estrogens measured in the serum of thirty pregnant women. Fractional receptor occupancy (FRO) based estrogenicity was dominated by E1, E2 and E3 (ER-a, 94.4–99.2% (median: 97.3%), ER-ß, 82.7–97.7% (median: 92.8%), as was the total response (TR), which included ligand specific differences in recruitment of co-activator proteins (RCA). The median FRO for BPA was at least fve orders of magnitude lower than E1, E2 and E3, and three orders of magnitude lower than the fetal derived E4 and GEN and DDZ. BPA contributed less than 1/1000th of the normal daily variability in total serum estrogenicity in this cohort of pregnant women.

Authors:
 [1];  [2];  [3];  [3]; ORCiD logo [3]; ORCiD logo [4]
  1. Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
  2. U.S. Food and Drug Administration, Jefferson, AR (United States); Fraunhofer Institute for Molecular Biology and Applied Ecology, Frankfurt am Main (Germany)
  3. U.S. Food and Drug Administration, Jefferson, AR (United States)
  4. Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Oregon State Univ., Corvallis, OR (United States)
Publication Date:
Research Org.:
Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
1511470
Report Number(s):
PNNL-ACT-SA-10390
Journal ID: ISSN 0278-6915
Grant/Contract Number:  
AC05-76RL01830
Resource Type:
Accepted Manuscript
Journal Name:
Food and Chemical Toxicology
Additional Journal Information:
Journal Volume: 125; Journal Issue: C; Journal ID: ISSN 0278-6915
Publisher:
Elsevier
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; Bisphenol A; Total estrogenicity; Estrogens; Pharmacokinetics; Exposure; Pregnancy; Biomonitoring; Endocrine disruptors

Citation Formats

Pande, Paritosh, Fleck, Stefanie C., Twaddle, Nathan C., Churchwell, Mona I., Doerge, Daniel R., and Teeguarden, Justin G. Comparative estrogenicity of endogenous, environmental and dietary estrogens in pregnant women II: Total estrogenicity calculations accounting for competitive protein and receptor binding and potency. United States: N. p., 2018. Web. doi:10.1016/j.fct.2018.12.013.
Pande, Paritosh, Fleck, Stefanie C., Twaddle, Nathan C., Churchwell, Mona I., Doerge, Daniel R., & Teeguarden, Justin G. Comparative estrogenicity of endogenous, environmental and dietary estrogens in pregnant women II: Total estrogenicity calculations accounting for competitive protein and receptor binding and potency. United States. doi:10.1016/j.fct.2018.12.013.
Pande, Paritosh, Fleck, Stefanie C., Twaddle, Nathan C., Churchwell, Mona I., Doerge, Daniel R., and Teeguarden, Justin G. Thu . "Comparative estrogenicity of endogenous, environmental and dietary estrogens in pregnant women II: Total estrogenicity calculations accounting for competitive protein and receptor binding and potency". United States. doi:10.1016/j.fct.2018.12.013. https://www.osti.gov/servlets/purl/1511470.
@article{osti_1511470,
title = {Comparative estrogenicity of endogenous, environmental and dietary estrogens in pregnant women II: Total estrogenicity calculations accounting for competitive protein and receptor binding and potency},
author = {Pande, Paritosh and Fleck, Stefanie C. and Twaddle, Nathan C. and Churchwell, Mona I. and Doerge, Daniel R. and Teeguarden, Justin G.},
abstractNote = {Evaluating the biological significance of human-relevant exposures to environmental estrogens involves assessing the individual and total estrogenicity of endogenous and exogenous estrogens found in serum, for example from biomonitoring studies. We developed a method for this assessment by integrating approaches for (i) measuring total hormone concentrations by mass spectrometry (Fleck et al., 2017), (ii) calculating hormone bioavailable concentrations in serum and, (iii) solving multiple equilibria between estrogenic ligands and receptors, and (iv) quantitatively describing key elements of estrogen potency. The approach was applied to endogenous (E1, E2,E3, E4), environmental (BPA), and dietary Genistein (GEN), Daidzein (DDZ) estrogens measured in the serum of thirty pregnant women. Fractional receptor occupancy (FRO) based estrogenicity was dominated by E1, E2 and E3 (ER-a, 94.4–99.2% (median: 97.3%), ER-ß, 82.7–97.7% (median: 92.8%), as was the total response (TR), which included ligand specific differences in recruitment of co-activator proteins (RCA). The median FRO for BPA was at least fve orders of magnitude lower than E1, E2 and E3, and three orders of magnitude lower than the fetal derived E4 and GEN and DDZ. BPA contributed less than 1/1000th of the normal daily variability in total serum estrogenicity in this cohort of pregnant women.},
doi = {10.1016/j.fct.2018.12.013},
journal = {Food and Chemical Toxicology},
number = C,
volume = 125,
place = {United States},
year = {2018},
month = {12}
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record

Save / Share: