Halogen-Bonding Interactions of Polybrominated Diphenyl Ethers and Thyroid Hormone Derivatives: A Potential Mechanism for the Inhibition of Iodothyronine Deiodinase

2017 ◽  
Vol 23 (27) ◽  
pp. 6625-6633 ◽  
Author(s):  
Eric S. Marsan ◽  
Craig A. Bayse
Keyword(s):  
Thyroid Hormone ◽  
Polybrominated Diphenyl Ethers ◽  
Halogen Bonding ◽  
Potential Mechanism ◽  
Iodothyronine Deiodinase ◽  
Diphenyl Ethers

In vitro assessment of potential mechanism-specific effects of polybrominated diphenyl ethers

2002 ◽  
Vol 21 (11) ◽  
pp. 2431-2433 ◽  
Author(s):  
Daniel L. Villeneuve ◽  
Kurunthachalam Kannan ◽  
Benjamin T. Priest ◽  
John P. Giesy
Keyword(s):  
Polybrominated Diphenyl Ethers ◽  
Potential Mechanism ◽  
Specific Effects ◽  
Diphenyl Ethers ◽  
In Vitro Assessment

scholarly journals A Halogen Bonding Perspective on Iodothyronine Deiodinase Activity

Molecules ◽  
2020 ◽  
Vol 25 (6) ◽  
pp. 1328 ◽  
Author(s):  
Eric S. Marsan ◽  
Craig A. Bayse
Keyword(s):  
Active Site ◽  
Polybrominated Diphenyl Ethers ◽  
Density Functional ◽  
Endocrine System ◽  
Halogen Bonding ◽  
Binding Energies ◽  
Active Site Residues ◽  
Iodothyronine Deiodinase ◽  
Donor Acceptor ◽  
Small Models

Iodothyronine deiodinases (Dios) are involved in the regioselective removal of iodine from thyroid hormones (THs). Deiodination is essential to maintain TH homeostasis, and disruption can have detrimental effects. Halogen bonding (XB) to the selenium of the selenocysteine (Sec) residue in the Dio active site has been proposed to contribute to the mechanism for iodine removal. Polybrominated diphenyl ethers (PBDEs) and polychlorinated biphenyls (PCBs) are known disruptors of various pathways of the endocrine system. Experimental evidence shows PBDEs and their hydroxylated metabolites (OH-BDEs) can inhibit Dio, while data regarding PCB inhibition are limited. These xenobiotics could inhibit Dio activity by competitively binding to the active site Sec through XB to prevent deiodination. XB interactions calculated using density functional theory (DFT) of THs, PBDEs, and PCBs to a methyl selenolate (MeSe−) arrange XB strengths in the order THs > PBDEs > PCBs in agreement with known XB trends. THs have the lowest energy C–X*-type unoccupied orbitals and overlap with the Se lp donor leads to high donor-acceptor energies and the greatest activation of the C–X bond. The higher energy C–Br* and C–Cl* orbitals similarly result in weaker donor-acceptor complexes and less activation of the C–X bond. Comparison of the I···Se interactions for the TH group suggest that a threshold XB strength may be required for dehalogenation. Only highly brominated PBDEs have binding energies in the same range as THs, suggesting that these compounds may inhibit Dio and undergo debromination. While these small models provide insight on the I···Se XB interaction itself, interactions with other active site residues are governed by regioselective preferences observed in Dios.

Polybrominated diphenyl ethers and thyroid hormone homeostasis in a New England cohort

2013 ◽  
Vol 2013 (1) ◽  
pp. 5180
Author(s):  
Colleen Makey ◽  
Michael McClean ◽  
Lewis Braverman ◽  
Elizabeth Pearce ◽  
Janice Weinberg ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
New England ◽  
Polybrominated Diphenyl Ethers ◽  
Diphenyl Ethers ◽  
Hormone Homeostasis

Impact of Polybrominated Diphenyl Ethers on Thyroid Hormone Levels Among California Women During Second Trimester of Pregnancy

Epidemiology ◽  
2011 ◽  
Vol 22 ◽  
pp. S161
Author(s):  
Ami Zota ◽  
Jackie Schwartz ◽  
Jody Steinauer ◽  
Myrto Petreas ◽  
Tanya Pasternack ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Polybrominated Diphenyl Ethers ◽  
Second Trimester ◽  
Hormone Levels ◽  
Diphenyl Ethers ◽  
Thyroid Hormone Levels

scholarly journals Halogen bonding from the bonding perspective with considerations for mechanisms of thyroid hormone activation and inhibition

2018 ◽  
Vol 42 (13) ◽  
pp. 10623-10632 ◽  
Author(s):  
Craig A. Bayse
Keyword(s):  
Thyroid Hormone ◽  
Thyroid Hormones ◽  
Halogen Bonding ◽  
Thyroid Activity ◽  
Iodothyronine Deiodinase

Bonding models of halogen bonding help understand how thyroid hormones and xenobiotic inhibitors affect thyroid activity through iodothyronine deiodinase.

scholarly journals PBDEs Concentrate in the Fetal Portion of the Placenta: Implications for Thyroid Hormone Dysregulation

Endocrinology ◽  
2019 ◽  
Vol 160 (11) ◽  
pp. 2748-2758 ◽  
Author(s):  
Matthew T Ruis ◽  
Kylie D Rock ◽  
Samantha M Hall ◽  
Brian Horman ◽  
Heather B Patisaul ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Mrna Expression ◽  
Neural Development ◽  
Polybrominated Diphenyl Ethers ◽  
Maternal Serum ◽  
Fetal Sex ◽  
Critical Window ◽  
Increased Risk ◽  
Diphenyl Ethers ◽  
Adverse Pregnancy

Abstract During pregnancy, the supply of thyroid hormone (TH) to the fetus is critically important for fetal growth, neural development, metabolism, and maintenance of pregnancy. Additionally, in cases where maternal and placental TH regulation is significantly altered, there is an increased risk of several adverse pregnancy outcomes. It is unclear what may be disrupting placental TH regulation; however, studies suggest that environmental contaminants, such as polybrominated diphenyl ethers (PBDEs), could be playing a role. In this study, Wistar rats were gestationally exposed to a mixture of PBDEs for 10 days. THs and PBDEs were quantified in paired maternal serum, dissected placenta, and fetuses, and mRNA expression of transporters in the placenta was assessed. Significantly higher concentrations of PBDEs were observed in the fetal portion of the placenta compared with the maternal side, suggesting that PBDEs are actively transported across the interface. PBDEs were also quantified in 10 recently collected human maternal and fetal placental tissues; trends paralleled observations in the rat model. We also observed an effect of PBDEs on T3 levels in dam serum, as well as suggestive changes in the T3 levels of the placenta and fetus that varied by fetal sex. mRNA expression in the placenta also significantly varied by fetal sex and dose. These observations suggest the placenta is a significant modifier of fetal exposures, and that PBDEs are impacting TH regulation in a sex-specific manner during this critical window of development.

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