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HERO ID
5618172
Reference Type
Journal Article
Title
Endocrine disruption: In silico interactions between phthalate plasticizers and corticosteroid binding globulin
Author(s)
Sheikh, IA; Beg, MA
Year
2017
Is Peer Reviewed?
Yes
Journal
Journal of Applied Toxicology
ISSN:
0260-437X
EISSN:
1099-1263
Publisher
WILEY
Location
HOBOKEN
Volume
37
Issue
12
Page Numbers
1471-1480
Language
English
PMID
28677244
DOI
10.1002/jat.3497
Web of Science Id
WOS:000413314000012
URL
https://search.proquest.com/docview/1916379443?accountid=171501
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Abstract
Endocrine disruption is a phenomenon when a man-made or natural compound interferes with normal hormone function in human or animal body systems. Endocrine-disrupting compounds (EDCs) have assumed considerable importance as a result of industrial activity, mass production of synthetic chemicals and environmental pollution. Phthalate plasticizers are a group of chemicals used widely and diversely in industry especially in the plastic industry, and many of the phthalate compounds have endocrine-disrupting properties. Increasing evidence indicates that steroid nuclear receptors and steroid binding proteins are the main targets of endocrine disruption. Corticosteroid-binding globulin (CBG) is a steroid binding protein that binds and transports cortisol in the blood circulation and is a potential target for endocrine disruption. An imbalance of cortisol in the body leads to many health problems. Induced fit docking of nine important and environmentally relevant phthalate plasticizers (DMP, BBP, DBP, DIBP, DnHP, DEHP, DINP, DnOP, DIDP) showed interactions with 10-19 amino acid residues of CBG. Comparison of the interacting residues of CBG with phthalate ligands and cortisol showed an overlapping of the majority (53-82%) of residues for each phthalate. Five of nine phthalate compounds and cortisol shared a hydrogen bonding interaction with the Arg-252 residue of CBG. Long-chain phthalates, such as DEHP, DINP, DnOP and DIDP displayed a higher binding affinity and formed a number of interactions with CBG in comparison to short-chain phthalates. The similarity in structural binding characteristics of phthalate compounds and native ligand cortisol suggested potential competitive conflicts in CBG-cortisol binding function and possible disruption of cortisol and progesterone homeostasis. Phthalates as endocrine-disrupting compounds (EDC) have assumed considerable importance as a result of environmental pollution. Corticosteroid-binding globulin (CBG) transports cortisol in the blood circulation and is a potential target for endocrine disruption. An imbalance of cortisol in the body leads to many health problems. Induced fit docking of important phthalate plasticizers revealed similarity in structural binding characteristics of phthalate compounds and native ligand cortisol. These results suggest competitive conflicts in CBG-cortisol binding function and potential disruption of cortisol homeostasis.
Keywords
corticosteroid‐binding globulin; docking; endocrine disruption; health problems; phthalates
Tags
IRIS
•
BBP (Butyl benzyl phthalate)
Literature Search
Literature Search: February 2017 - July 2017
Pubmed
•
Dibutyl Phthalate (DBP)
Database Searches
LitSearch Jan 2017 - July 2017
Pubmed
LitSearch July 2017 - Sept 2018
Prior Search Overlap
WOS
•
Diisobutyl Phthalate (DIBP) Final
Database Searches
July 2017 Update
PubMed
New for this search
Studies with Supporting Data
Mechanistic and genotoxicity studies
•
Diisononyl Phthalate (DINP)
Literature Search
LitSearch Jan 2017 - July 2017 Update
Considered new
PubMed
•
Phthalates – Targeted Search for Epidemiological Studies
Source – all searches
Pubmed
Toxnet
Excluded
Source - August 2017 Update (Private)
Pubmed
Toxnet
Source - August 2018 Update
Pubmed
WOS
Toxline
Level 1 Screen - Title & Abstract
Excluded
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