1,720,994 research outputs found
Effects of prenatal exposure to low doses of diethylstilbestrol, o,p' DDT and methoxychlor on postnatal growth and neurobehavioral development in male and female mice
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Ethological methods to assess the impact of estrogenic endocrine disruptors on behavior: a study with methoxychlor
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Identification of putative steroid receptor antagonists in bottled water : combining bioassays and high-resolution mass spectrometry
No full textEndocrine disrupting chemicals (EDCs) are man-made compounds interfering with hormone signaling and thereby adversely affecting human health. Recent reports provide evidence for the presence of EDCs in commercially available bottled water, including steroid receptor agonists and antagonists. However, since these findings are based on biological data the causative chemicals remain unidentified and, therefore, inaccessible for toxicological evaluation. Thus, the aim of this study is to assess the antiestrogenic and antiandrogenic activity of bottled water and to identify the causative steroid receptor antagonists. We evaluated the antiestrogenic and antiandrogenic activity of 18 bottled water products in reporter gene assays for human estrogen receptor alpha and androgen receptor. Using nontarget high-resolution mass spectrometry (LTQ-Orbitrap Velos), we acquired corresponding analytical data. We combined the biological and chemical information to determine the exact mass of the tentative steroid receptor antagonist. Further MS(n) experiments elucidated the molecule's structure and enabled its identification. We detected significant antiestrogenicity in 13 of 18 products. 16 samples were antiandrogenic inhibiting the androgen receptor by up to 90%. Nontarget chemical analysis revealed that out of 24520 candidates present in bottled water one was consistently correlated with the antagonistic activity. By combining experimental and in silico MS(n) data we identified this compound as di(2-ethylhexyl) fumarate (DEHF). We confirmed the identity and biological activity of DEHF and additional isomers of dioctyl fumarate and maleate using authentic standards. Since DEHF is antiestrogenic but not antiandrogenic we conclude that additional, yet unidentified EDCs must contribute to the antagonistic effect of bottled water. Applying a novel approach to combine biological and chemical analysis this is the first study to identify so far unknown EDCs in bottled water. Notably, dioctyl fumarates and maleates have been overlooked by science and regulation to date. This illustrates the need to identify novel toxicologically relevant compounds to establish a more holistic picture of the human exposome
Steroid Hormones and Endocrine Disruptors: Recent Advances in Receptor–Mediated Actions
Get PDFIt has been accepted that receptor-mediated action of steroid hormones depends on
both the receptor and the hormonal level. The mechanism of transcription by steroid
receptors is mediated by cofactors, which function as co-activators or co-repressors,
while their non-genomic actions depend on receptors localized to the cell membrane.
Recently, a number of environmental chemicals, which are now termed as endocrine
disruptors, have been identified, and their unwanted effects on our lives have become
serious problems all over the world. Their adverse effects on endocrine systems in
animals, mostly estrogenic or anti-estrogenic, have resulted in reproductive malfunction
and developmental disorders. Although aryl hydrocarbons exhibit estrogenic or anti-
estrogenic activity through specific interaction with aryl hydrocarbon receptors, other
chemicals seem to interact directly with estrogen receptors, α and β forms. In this
paper, we surveyed the most recent understanding of endocrine disruptors from the
viewpoint of steroid receptor systems. We suggest two potential mechanisms of action
for endocrine disruptors. Endocrine distruptors i) directly associate with steroid
receptor systems and/or ii) associate with the growth factor or the neurotransmitter
receptor systems, and then upregulate the mitogen-activated protein kinase signaling
cascades, leading to the ligand-independent activation of steroid receptor systems. Using
these steroid receptor-dependent mechanisms, it appears that endocrine disruptors
disorder our endocrine systems. We have proposed future suggestions to further
understand endocrine disruptors from the viewpoint of steroid receptor systems.
Key words: endocrine disruptors; receptor-mediated actions; steroid hormone
Steroid Hormones and Endocrine Disruptors: Recent Advances in Receptor–Mediated Actions
Get PDFIt has been accepted that receptor-mediated action of steroid hormones depends on
both the receptor and the hormonal level. The mechanism of transcription by steroid
receptors is mediated by cofactors, which function as co-activators or co-repressors,
while their non-genomic actions depend on receptors localized to the cell membrane.
Recently, a number of environmental chemicals, which are now termed as endocrine
disruptors, have been identified, and their unwanted effects on our lives have become
serious problems all over the world. Their adverse effects on endocrine systems in
animals, mostly estrogenic or anti-estrogenic, have resulted in reproductive malfunction
and developmental disorders. Although aryl hydrocarbons exhibit estrogenic or anti-
estrogenic activity through specific interaction with aryl hydrocarbon receptors, other
chemicals seem to interact directly with estrogen receptors, α and β forms. In this
paper, we surveyed the most recent understanding of endocrine disruptors from the
viewpoint of steroid receptor systems. We suggest two potential mechanisms of action
for endocrine disruptors. Endocrine distruptors i) directly associate with steroid
receptor systems and/or ii) associate with the growth factor or the neurotransmitter
receptor systems, and then upregulate the mitogen-activated protein kinase signaling
cascades, leading to the ligand-independent activation of steroid receptor systems. Using
these steroid receptor-dependent mechanisms, it appears that endocrine disruptors
disorder our endocrine systems. We have proposed future suggestions to further
understand endocrine disruptors from the viewpoint of steroid receptor systems.
Key words: endocrine disruptors; receptor-mediated actions; steroid hormone
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