TY - JOUR
T1 - Characterization of Estrogenic and Androgenic Activities for Bisphenol A-like Chemicals (BPs)
T2 - In Vitro Estrogen and Androgen Receptors Transcriptional Activation, Gene Regulation, and Binding Profiles
AU - Pelch, Katherine E.
AU - Li, Yin
AU - Perera, Lalith
AU - Thayer, Kristina A.
AU - Korach, Kenneth S.
N1 - Funding Information:
This work was supported by the National Institute of Environmental Health Sciences.
Publisher Copyright:
© 2019 The Author(s) 2019. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
PY - 2019/11/1
Y1 - 2019/11/1
N2 - Bisphenol A (BPA) is a high production volume chemical widely used in plastics, food packaging, and many other products. It is well known that endocrine-disrupting chemicals might be harmful to human health due to interference with normal hormone actions. Recent studies report widespread usage and exposure to many BPA-like chemicals (BPs) that are structurally or functionally similar to BPA. However, the biological actions and toxicity of those BPs are still relatively unknown. To address this data gap, we used in vitro cell models to evaluate the ability of 22 BPs to induce or inhibit estrogenic and androgenic activity. BPA, Bisphenol AF (BPAF), bisphenol Z (BPZ), bisphenol C (BPC), tetramethyl bisphenol A (TMBPA), bisphenol S (BPS), bisphenol E (BPE), 4,4-bisphenol F (4,4-BPF), bisphenol AP (BPAP), bisphenol B (BPB), tetrachlorobisphenol A (TCBPA), and benzylparaben (PHBB) induced estrogen receptor (ER)α and/or ERβ-mediated activity. With the exception of BPS, TCBPA, and PHBB, these same BPs were also androgen receptor (AR) antagonists. Only 3 BPs were found to be ER antagonists. Bisphenol P (BPP) selectively inhibited ERβ-mediated activity and 4-(4-phenylmethoxyphenyl)sulfonylphenol (BPS-MPE) and 2,4-bisphenol S (2,4-BPS) selectively inhibited ERα-mediated activity. None of the BPs induced AR-mediated activity. In addition, we identify that the BPs can bind to ER or AR with varying degrees by a molecular modeling analysis. Taken together, these findings help us to understand the molecular mechanism of BPs and further consideration of their usage in consumer products.
AB - Bisphenol A (BPA) is a high production volume chemical widely used in plastics, food packaging, and many other products. It is well known that endocrine-disrupting chemicals might be harmful to human health due to interference with normal hormone actions. Recent studies report widespread usage and exposure to many BPA-like chemicals (BPs) that are structurally or functionally similar to BPA. However, the biological actions and toxicity of those BPs are still relatively unknown. To address this data gap, we used in vitro cell models to evaluate the ability of 22 BPs to induce or inhibit estrogenic and androgenic activity. BPA, Bisphenol AF (BPAF), bisphenol Z (BPZ), bisphenol C (BPC), tetramethyl bisphenol A (TMBPA), bisphenol S (BPS), bisphenol E (BPE), 4,4-bisphenol F (4,4-BPF), bisphenol AP (BPAP), bisphenol B (BPB), tetrachlorobisphenol A (TCBPA), and benzylparaben (PHBB) induced estrogen receptor (ER)α and/or ERβ-mediated activity. With the exception of BPS, TCBPA, and PHBB, these same BPs were also androgen receptor (AR) antagonists. Only 3 BPs were found to be ER antagonists. Bisphenol P (BPP) selectively inhibited ERβ-mediated activity and 4-(4-phenylmethoxyphenyl)sulfonylphenol (BPS-MPE) and 2,4-bisphenol S (2,4-BPS) selectively inhibited ERα-mediated activity. None of the BPs induced AR-mediated activity. In addition, we identify that the BPs can bind to ER or AR with varying degrees by a molecular modeling analysis. Taken together, these findings help us to understand the molecular mechanism of BPs and further consideration of their usage in consumer products.
KW - androgen receptor
KW - binding
KW - bisphenol analogs
KW - estrogen receptor
KW - gene regulation
KW - transcriptional activation
UR - http://www.scopus.com/inward/record.url?scp=85082003244&partnerID=8YFLogxK
U2 - 10.1093/toxsci/kfz173
DO - 10.1093/toxsci/kfz173
M3 - Article
C2 - 31388671
AN - SCOPUS:85082003244
SN - 1096-6080
VL - 172
SP - 23
EP - 37
JO - Toxicological Sciences
JF - Toxicological Sciences
IS - 1
ER -