Disruption of glucocorticoid action by environmental chemicals: Potential mechanisms and relevance

Odermatt, Alex; Gumy, Christel; Atanasov, Atanas G.; Dzyakanchuk, Anna

doi:10.1016/j.jsbmb.2006.09.010

Cited by 69 publications

(50 citation statements)

References 123 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…It is reasonable to expect that exposure to environmental chemicals that can directly stimulate the HPA axis, activate GR, alter GR function, or elevate the peripheral levels of endogenous GR ligands may be contributing factors for metabolic complications. Indeed, an extensive and chemically diverse group of compounds have been reported that serve as examples of environmental agents able to elevate or depress glucocorticoid signaling (reviewed in [91]). …”

Section: Organotinsmentioning

confidence: 99%

Perturbed nuclear receptor signaling by environmental obesogens as emerging factors in the obesity crisis

Grün

Blumberg

2007

Rev Endocr Metab Disord

265

178

View full text Add to dashboard Cite

The modern world is plagued with expanding epidemics of diseases related to metabolic dysfunction. The factors that are driving obesity, diabetes, cardiovascular disease, hypertension, and dyslipidemias (collectively termed metabolic syndrome) are usually ascribed to a mismatch between the body's homeostatic nutrient requirements and dietary excess, coupled with insufficient exercise. The environmental obesogen hypothesis proposes that exposure to a toxic chemical burden is superimposed on these conditions to initiate or exacerbate the development of obesity and its associated health consequences. Recent studies have proposed a first set of candidate obesogens (diethylstilbestrol, bisphenol A, phthalates and organotins among others) that target nuclear hormone receptor signaling pathways (sex steroid, RXR-PPARgamma and GR) with relevance to adipocyte biology and the developmental origins of health and disease (DOHaD). Perturbed nuclear receptor signaling can alter adipocyte proliferation, differentiation or modulate systemic homeostatic controls, leading to long-term consequences that may be magnified if disruption occurs during sensitive periods during fetal or early childhood development.

show abstract

Section: Organotinsmentioning

confidence: 99%

Perturbed nuclear receptor signaling by environmental obesogens as emerging factors in the obesity crisis

Grün

Blumberg

2007

Rev Endocr Metab Disord

265

178

View full text Add to dashboard Cite

show abstract

“…Nuclear receptor translocation is an important indicator of nuclear receptor function and can be measured in HTS and HCS platforms in order to study the mechanism of compound action. Environmental chemicals including polychlorinated biphenyls (PCBs), PAHs, and heavy metals have been shown to disrupt GR signalling and increase health risk (Odermatt et al, 2006). A cell-based β-galactosidase fragment complementation assay of GR translocation was validated in a 1,536-well format and applied to a qHTS screen .…”

Section: Nuclear Receptor Assaysmentioning

confidence: 99%

Advances in high-throughput screening technology for toxicology

Hsu

Huang

Attene‐Ramos

et al. 2017

IJRAM

View full text Add to dashboard Cite

Abstract:The US Tox21 collaboration utilises a quantitative high-throughput screening (qHTS) platform to efficiently profile a large number of environmental chemicals. qHTS combined with informatics facilitates chemical prioritisation for further in-depth toxicity testing and development of computational models to predict chemical toxicity. The NIH Chemical Genomics Center (NCGC), now part of the National Center for Advancing Translational Sciences (NCATS), is a key contributor during all phases of the Tox21 collaboration, from assay development and compound screening to data analysis and model building. Since 2011, the Tox21/NCGC has been profiling the phase 2 Tox21 library of approximately 10,000 (10K) environmental chemicals and drugs. The advances in HTS assays and qHTS screens against the Tox21's and other chemical libraries are described in this review.

show abstract

“…[16] As a starting point to identify chemicals that act on different steps of glucocorticoid and mineralocorticoid regulation, we established assays to measure the function of human corticosteroid hormone receptors (GR and MR) and glucocorticoid metabolizing enzymes (11β -HSD1 and 11β -HSD2). To distinguish between different steps of receptor activation, the HEK-293 cell line was selected that is devoid of endogenous expression of corticosteroid receptors and hormone metabolizing enzymes.…”

Section: Bioassaysmentioning

confidence: 99%

Disruption of Glucocorticoid and Mineralocorticoid Receptor-Mediated Responses by Environmental Chemicals

Odermatt¹,

Gumy²

2008

Chimia

Self Cite

View full text Add to dashboard Cite

Glucocorticoids and mineralocorticoids are key endocrine hormones modulating essential physiological processes such as energy metabolism, cell growth and differentiation, maintenance of blood pressure and immune responses. Despite their importance and the fact that their impaired function has been associated with various diseases, there are only few studies on the potential disruption of glucocorticoid and mineralocorticoid action by xenobiotics. To facilitate the identification and characterization of such chemicals, we established cell-based assays to determine the impact of xenobiotics on different steps of corticosteroid hormone action. Screening of a small library of chemicals led to the identification of several compounds inhibiting the 11β -hydroxysteroid dehydrogenase (11β -HSD) prereceptor enzymes 11β -HSD1 and/or 11β -HSD2 and of chemicals blocking the function of glucocorticoid receptors (GR) and mineralocorticoid receptors (MR). These findings build a basis to extend the search for chemicals acting on additional targets of the corticosteroid hormone pathway and to apply in silico prediction tools in combination with biological testing to screen large numbers of chemicals. The identification of chemicals interfering with corticosteroid action and the elucidation of the underlying molecular mechanisms are relevant with respect to the potential contribution to common diseases such as metabolic syndrome, immune diseases, brain disorders and cancer.

show abstract

Disruption of glucocorticoid action by environmental chemicals: Potential mechanisms and relevance

Cited by 69 publications

References 123 publications

Perturbed nuclear receptor signaling by environmental obesogens as emerging factors in the obesity crisis

Perturbed nuclear receptor signaling by environmental obesogens as emerging factors in the obesity crisis

Advances in high-throughput screening technology for toxicology

Disruption of Glucocorticoid and Mineralocorticoid Receptor-Mediated Responses by Environmental Chemicals

Contact Info

Product

Resources

About