Review on crosstalk and common mechanisms of endocrine disruptors: Scaffolding to improve PBPK/PD model of EDC mixture. (February 2017)

• Record Type: Journal Article
• Authors: Sharma, Raju Prasad; Schuhmacher, Marta; Kumar, Vikas
• Is Part Of: Environment international. Volume 99(2017:Feb.)
• Page Start: 1
• Page End: 14
• Publication Date: 2017-02
• Subjects: 3MC 3-methylcholanthrene -- 5α-R 5-alpha reductase -- ACTH adrenocorticotropic hormone -- Ahr aryl hydrocarbon receptor -- Ahrr aryl hydrocarbon receptor repressor -- AKT serine/threonine kinase -- AMH anti-mullerian hormone -- AMPO ammonium perfluorooctane -- ARC arcuate cell -- Arnt aryl nuclear translocator -- AVPV anteroventral periventricular nucleus -- BAX BCL2 associated protein -- BCL2 apoptosis regulator -- BMP bone morphogenetic protein -- BPA bisphenol A -- CAR constitutive androstane receptor -- CREB cAMP response-element–binding protein -- Cx43 connexin X 43 -- CYP1A1 cytochrome enzyme A -- CYP1B1 cytochrome enzyme B -- CYP19A aromatase enzyme -- CYP450scc cytochrome p450 side chain cleavage -- DBT dibutyltin -- DEHP diethylhexyl phthalate -- DTCs dithiocarbamate chemicals -- ERE estrogen response element -- E2 estrogen -- FAK focal adhesion kinase -- Fas membrane protein -- FasL fas ligand -- Figla factor in the germline alpha -- FOXO3 forkhead box proteins -- FSH follicle stimulating hormone -- GATA4 transcription factor -- GDF growth differentiation factor -- GH growth hormone -- GJ gap junction -- GJA1 gap junction alpha protein -- GnRH gonadotropin releasing hormone -- GVBD germinal vesicle migration and breakdown -- HAT histone acetyl-transferase -- HPA hypothalamus pituitary adrenal axis -- HDAC histone deacetylases -- HMT histone methyl transferase -- HPOA hypothalamus preoptic nucleus -- HSDs hydroxysteroid dehydrogenases -- HSP90 heat shock protein 90 -- IGF-1 insulin growth factor -- IGFR insulin growth factor receptor -- Igf2r insulin like growth factor 2 -- INH inhibin -- IP3-DAG inositol triphosphate-diacylglycerol -- LH luteinizing hormone -- LHR luteinizing hormone receptor -- LHX8 LIM homeobox 8 -- LXR liver X receptor -- LXR liver X receptor -- MAPK mitogen activated protein kinase -- MEHP mono (2-ethylhexyl) phthalate -- MMP2 metalloproteinase 2 -- NCoA nuclear coactivator -- NCoR nuclear corepressor -- NF-kB nuclear factor k B -- NOBOX newborn ovary homeobox -- NR notch receptor -- p160/SRC steroid receptor coactivator -- P23 protein 23 -- P4 progesterone -- PR progesterone receptor -- PBPK/PD physiological based pharmacokinetic/pharmacodynamic modeling -- PBR peripheral type Benzodiazepine receptor -- PCBs polychlorinated biphenyl -- PCDDs polychlorinated dibenzodioxins -- Peg3 paternal express gene 3 -- PEPCK phosphoenolpyruvate carboxykinase -- PFASs poly-fluorinated alkyl substances -- PI3 phosphatidylinositol 3-kinase -- PMG primordial germ cell -- PPARs peroxisome proliferator activated receptors -- PTEN phosphatase and tensin homolog -- PXR pregnane X receptor -- RIP140 receptor interacting protein -- ROS reactive oxygen species -- RXR retinoid X receptor -- SDM sexual dimorphism -- SF 1-steroidogenesis factor 1 -- SHBG steroid hormone binding globulin -- SMRT silencing mediator for retinoid or thyroid-hormone receptors -- Sohlh2 spermatogenesis and oogenesis helix-loop-helix 2 -- SREBP 2 sterol Response Element Binding Protein 2 -- SREBP1c sterol Response Element Binding Protein 1c -- StAR steroid acute regulatory protein -- SUG 1 suppressor for gal 1 -- SULTs sulphotransferase enzyme -- TAT tyrosine aminotransferase -- TBG thyroid binding globulin -- TBT tributyltin -- TCDD 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin -- TCPOBOP 1, 4-bis[2-(3, 5-dichloropyridyloxy)] benzene -- TH thyroid hormone -- TJ tight junction -- TNF α tumor necrosis factor α -- TPT triphenyltin -- TRAIL TNF-related apoptosis-inducing ligand -- TRs thyroid receptors -- TSPO translocator protein -- UDPGT1A1 uridine diphosphate glucuronic transferase enzyme -- VCL vocal adhesion molecule vinculin -- VEGF vascular endothelial growth factor -- VTG vitellogenin -- XAP2 X-associated protein 2 -- ZO-1 zonula occludens-1; Endocrine disruptor compounds (EDCs) -- Toxicity mechanism -- Mixture interaction -- Common mechanism -- Crosstalk -- PBPK/PD models; Environmental protection -- Periodicals; Environmental health -- Periodicals; Environmental monitoring -- Periodicals; Environmental Monitoring -- Periodicals; Environnement -- Protection -- Périodiques; Hygiène du milieu -- Périodiques; Environnement -- Surveillance -- Périodiques; Environmental health; Environmental monitoring; Environmental protection; Periodicals; 333.705
• DOI: 10.1016/j.envint.2016.09.016
• Languages: English
• ISSNs: 0160-4120

Abstract

Abstract: Endocrine disruptor compounds (EDCs) are environment chemicals that cause harmful effects through multiple mechanisms, interfering with hormone system resulting in alteration of homeostasis, reproduction and developmental effect. Many of these EDCs have concurrent exposure with crosstalk and common mechanisms which may lead to dynamic interactions. To carry out risk assessment of EDCs' mixture, it is important to know the detailed toxic pathway, crosstalk of receptor and other factors like critical window of exposure. In this review, we summarize the major mechanism of actions of EDCs with the different/same target organs interfering with the same/different class of hormone by altering their synthesis, metabolism, binding and cellular action. To show the impact of EDCs on life stage development, a case study on female fertility affecting germ cell is illustrated. Based on this summarized discussion, major groups of EDCs are classified based on their target organ, mode of action and potential risk. Finally, a conceptual model of pharmacodynamic interaction is proposed to integrate the crosstalk and common mechanisms that modulate estrogen into the predictive mixture dosimetry model with dynamic interaction of mixture. This review will provide new insight for EDCs' risk assessment and can be used to develop next generation PBPK/PD models for EDCs' mixture analysis. Highlights: EDCs' mechanism involves multiple targets interfering hormone synthesis, metabolism and their biological action. Toxicodynamic interactions like crosstalk and common mechanisms are very important for elucidating the mixture effect. Window of exposure plays an important role in assessing the risk for developmental and reproductive disorders. In silico risk prediction can be improved by integrating toxicodynamic interactions of EDCs.