scholarly journals The different effects of endocrine-disrupting chemicals on estrogen receptor-mediated transcription through interaction with coactivator TRAP220 in uterine tissue

2003 ◽  
Vol 31 (3) ◽  
pp. 551-561 ◽  
Author(s):  
H Inoshita ◽  
H Masuyama ◽  
Y Hiramatsu

An endocrine-disrupting chemical (EDC) can alter endocrine functions through a variety of mechanisms, including nuclear receptor-mediated changes in protein synthesis, interference with membrane receptor binding, steroidogenesis or synthesis of other hormones. Although major chemicals have been shown to disrupt estrogenic actions mainly through their binding to estrogen receptor (ER) or androgen receptor, it is not clear how EDCs affect endocrine functions in vivo. We present evidence that the EDCs bisphenol A and phthalate activate ER-mediated transcription through interaction with TRAP220. Moreover, bisphenol A had positive effects on the interaction between ER-beta and TRAP220 and on the expression of ER-beta and TRAP220 compared with phthalate and estradiol in uterine tIssue. These data suggested that some EDCs might alter endocrine function through the change of the receptor and coactivator levels in uterine tIssue and through the different effect on the interaction between ERs and coactivator TRAP220.

Bioimpacts ◽  
2020 ◽  
Vol 11 (4) ◽  
pp. 289-300
Author(s):  
Sofiane Boudalia ◽  
Aissam Bousbia ◽  
Boualem Boumaaza ◽  
Malha Oudir ◽  
Marie Chantal Canivenc Lavier

Introduction: Scientific data suggest that early exposure to endocrine-disrupting chemicals (EDCs) affect -repro, -neuro, -metabolic systems, to which are added other notions such as mixtures, window and duration of exposure, trans-generational effects, and epigenetic mechanisms. Methods: In the present narrative review, we studied the relationship between exposure to EDCs with the appearance and development of obesity. Results: Exposure to EDCs like Bisphenol A during the early stages of development has been shown to lead to weight gain and obesity. EDCs can interfere with endocrine signaling, affect adipocytes differentiation and endocrine function and disrupt metabolic processes, especially if exposure occurs at very low doses, in the mixture, during early development stages for several generations. Conclusion: Exposure to EDCs is positively associated with obesity development. Moreover, the use of integrative approaches which mimicking environmental conditions are necessary and recommended to evaluate EDCs' effects in future studies.


Endocrinology ◽  
2016 ◽  
Vol 157 (4) ◽  
pp. 1408-1420 ◽  
Author(s):  
Kirsten S. Eckstrum ◽  
Karen E. Weis ◽  
Nicholas G. Baur ◽  
Yoshihiro Yoshihara ◽  
Lori T. Raetzman

Abstract Endocrine-disrupting chemicals are prevalent in the environment and can impair reproductive success by affecting the hypothalamic-pituitary-gonadal axis. The developing pituitary gland is sensitive to exposure to endocrine-disrupting chemicals, such as bisphenol A (BPA), and sex-specific effects can occur. However, effects on the critical window of neonatal pituitary gland development in mice have not been explored. Therefore, this study determined baseline gene expression in male and female pituitaries and consequences of environmental exposure to 17β-estradiol (E2) and BPA on transcription of genes exhibiting sex differences during the neonatal period. Through microarray and quantitative RT-PCR analysis of pituitaries at postnatal day (PND)1, 3 genes were differentially expressed between males and females: Lhb, Fshb, and intracellular adhesion molecule-5 (Icam5). To see whether E2 and BPA exposure regulates these genes, pituitaries were cultured at PND1 with 10−8M E2 or 4.4 × 10−6M BPA. E2 decreased expression of Lhb, Fshb, and Icam5 mRNA in females but only significantly decreased expression of Icam5 in males. BPA decreased expression of Icam5 similarly to E2, but it did not affect Lhb or Fshb. Importantly, in vivo exposure to 50-μg/kg · d E2 from PND0 to PND7 decreased expression of Lhb, Fshb, and Icam5 mRNA in both males and females, whereas 50-mg/kg · d BPA exposure during the same time frame decreased expression of Icam5 in females only. Overall, we have uncovered that genes differentially expressed between the sexes can be regulated in part by hormonal and chemical signals in vivo and directly at the pituitary and can be regulated in a sex-specific manner.


2020 ◽  
Vol 2 (4) ◽  
pp. 89-94
Author(s):  
Nikola Knizatova ◽  
Katarína Tokárová ◽  
Hana Greifová ◽  
Tomáš Jambor ◽  
Peter Massányi ◽  
...  

Bisphenol A (BPA) is the most well-known compound from the bisphenol family. There is increasing evidence that bisphenol BPA used in plastics, receipts, food packaging, and other products might be harmful to human health due to its actions as an endocrine-disrupting chemical, therefore BPA is being replaced by compounds very similar in structure, but data on the occurrence and effects of these BPA analogs are limited. Therefore, there is increasing concern regarding human exposure to bisphenol analogs (BPs) due to their widespread use and potential adverse effects. The main objective of this work was to investigate human exposure to BPs and the associated endocrine activities. We performed a literature review of the available research made in humans, in in vivo and in vitro tests. The findings support the idea that exposure to BPs may have an impact on human health, especially in terms of endocrine disruption.


Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Sarah Lindsey ◽  
Melyssa Bratton ◽  
John A McLachlan

We previously showed that activation of the membrane estrogen receptor GPR30 decreases blood pressure in hypertensive ovariectomized mRen2.Lewis rats and acutely dilates mesenteric resistance arteries. These studies suggest that GPR30 plays a role in estrogen’s beneficial cardiovascular effects. Bisphenol A (BPA) is an endocrine-disrupting chemical found in most manufactured plastic products that also binds to GPR30 in the nanomolar range. Clinical studies show a significant correlation between elevated urinary BPA and increased diagnosis of cardiovascular diseases including hypertension. Therefore, we hypothesized that BPA may disrupt the vasodilatory effects mediated by the novel estrogen receptor GPR30. Second-order mesenteric arteries from 15 week-old Lewis females were denuded and mounted on a wire myograph. Arteries were preconstricted with 10 μM phenylephrine before assessing the response to increasing concentrations of the selective GPR30 agonist G-1 (0.001-3 μM). Pretreatment with 10 μM BPA significantly inhibited G-1-induced relaxation of denuded vessels (Figure, *P<0.01). In summary, BPA blocked the vasodilatory actions of G-1 in vascular smooth muscle, perhaps by competing for GPR30 and/or altering its downstream signaling. We conclude that human exposure to BPA may interfere with the protective estrogenic effects mediated by GPR30.


2020 ◽  
Vol 9 (2) ◽  
pp. 405 ◽  
Author(s):  
Sophie-Christine de Aguiar Greca ◽  
Ioannis Kyrou ◽  
Ryan Pink ◽  
Harpal Randeva ◽  
Dimitris Grammatopoulos ◽  
...  

Background: Endocrine-disrupting chemicals (EDCs) are environmental chemicals/toxicants that humans are exposed to, interfering with the action of multiple hormones. Bisphenol A (BPA) is classified as an EDC with xenoestrogenic activity with potentially adverse effects in reproduction. Currently, a significant knowledge gap remains regarding the complete spectrum of BPA-induced effects on the human placenta. As such, the present study examined the effects of physiologically relevant doses of BPA in vitro. Methods: qRT-PCR, Western blotting, immunofluorescence, ELISA, microarray analyses, and bioinformatics have been employed to study the effects of BPA using nonsyncytialised (non-ST) and syncytialised (ST) BeWo cells. Results: Treatment with 3 nM BPA led to an increase in cell number and altered the phosphorylation status of p38, an effect mediated primarily via the membrane-bound estrogen receptor (GPR30). Nonbiased microarray analysis identified 1195 and 477 genes that were differentially regulated in non-ST BeWo cells, whereas in ST BeWo cells, 309 and 158 genes had altered expression when treated with 3 and 10 nM, respectively. Enriched pathway analyses in non-ST BeWo identified a leptin and insulin overlap (3 nM), methylation pathways (10 nM), and differentiation of white and brown adipocytes (common). In the ST model, most significantly enriched were the nuclear factor erythroid 2-related factor 2 (NRF2) pathway (3 nM) and mir-124 predicted interactions with cell cycle and differentiation (10 nM). Conclusion: Collectively, our data offer a new insight regarding BPA effects at the placental level, and provide a potential link with metabolic changes that can have an impact on the developing fetus.


2017 ◽  
Author(s):  
Robin B. Gear ◽  
Scott M. Belcher

ABSTRACTThe endocrine disruptor bisphenol A (BPA) and the pharmaceutical 17α-ethinyl estradiol (EE) are synthetic chemicals with estrogen-like activities. Despite ubiquitous human exposure to BPA, and the wide-spread clinical use of EE as oral contraceptive adjuvant, the impact of these estrogenic endocrine disrupting chemicals (EDCs) on the immune system is unclear. Here we report results of in vivo dose response studies that analyzed the histology and microstructural changes in the spleen of adult male and female CD-1 mice exposed to 4 to 40,000 μg/kg/day BPA or 0.02 to 2 μg/kg/day EE from conception until 12-14 weeks of age. Results of that analysis indicate that both BPA and EE have dose- and sex-specific impacts on the cellular and microanatomical structures of the spleens that reveal minor alterations in immunomodulatory and hematopoietic functions. These findings support previous studies demonstrating the murine immune system as a sensitive target for estrogens, and that oral exposures to BPA and EE can have estrogen-like immunomodulatory affects in both sexes.


2021 ◽  
Author(s):  
Angelica Amorim Amato ◽  
Hailey Britt Wheeler ◽  
Bruce Blumberg

Obesity is now a worldwide pandemic. The usual explanation given for the prevalence of obesity is that it results from consumption of a calorie dense diet coupled with physical inactivity. However, this model inadequately explains rising obesity in adults and in children over the past few decades, indicating that other factors must be important contributors. An Endocrine-Disrupting Chemical (EDC) is an exogenous chemical, or mixture that interferes with any aspect of hormone action. EDCs have become pervasive in our environment, allowing humans to be exposed daily through ingestion, inhalation, and direct dermal contact. Exposure to EDCs has been causally linked with obesity in model organisms and associated with obesity occurrence in humans. Obesogens are chemicals, including some EDCs that promote adipogenesis and obesity, in vivo, by a variety of mechanisms. The environmental obesogen model holds that exposure to obesogens elicits a predisposition to obesity and that such exposures may be an important yet overlooked factor in the obesity pandemic. Effects produced by EDCs and obesogen exposure may be passed to subsequent, unexposed generations. This “generational toxicology” is not currently factored into risk assessment by regulators but may be another important factor in the obesity pandemic as well as in the worldwide increases in the incidence of noncommunicable diseases that plague populations everywhere. This review addresses the current evidence on how obesogens affect body mass, discusses long-known chemicals that have been more recently identified as obesogens, and how the accumulated knowledge can help identify EDCs hazards.


2010 ◽  
Vol 3 (4) ◽  
pp. 385-401 ◽  
Author(s):  
M. Metzler ◽  
E. Pfeiffer ◽  
A. Hildebrand

Zearalenone (ZEA) is a macrocyclic β-resorcylic acid lactone produced by numerous species of Fusarium. It frequently contaminates corn and cereal products in many regions of the world. The biological activity of ZEA is dominated by its pronounced oestrogenicity, which is even enhanced in certain reductive metabolites. This review updates the metabolism in fungi, plants and mammalian systems, as well as the pharmacokinetics of ZEA. The present evidence for the hormonal effects of the parent mycoestrogen and some of its metabolites in vitro and in farm and experimental animals in vivo is reviewed, together with its association with endocrine-disruptive effects in humans. Possible mechanisms of the oestrogenic and carcinogenic activity of ZEA are discussed and future areas of research proposed.


2015 ◽  
Vol 54 (3) ◽  
pp. 289-303 ◽  
Author(s):  
Ciro Menale ◽  
Maria Teresa Piccolo ◽  
Grazia Cirillo ◽  
Raffaele A Calogero ◽  
Alfonso Papparella ◽  
...  

Bisphenol A (BPA) is a xenobiotic endocrine-disrupting chemical.In vitroandin vivostudies have indicated that BPA alters endocrine-metabolic pathways in adipose tissue, which increases the risk of metabolic disorders and obesity. BPA can affect adipose tissue and increase fat cell numbers or sizes by regulating the expression of the genes that are directly involved in metabolic homeostasis and obesity. Several studies performed in animal models have accounted for an obesogen role of BPA, but its effects on human adipocytes – especially in children – have been poorly investigated. The aim of this study is to understand the molecular mechanisms by which environmentally relevant doses of BPA can interfere with the canonical endocrine function that regulates metabolism in mature human adipocytes from prepubertal, non-obese children. BPA can act as an estrogen agonist or antagonist depending on the physiological context. To identify the molecular signatures associated with metabolism, transcriptional modifications of mature adipocytes from prepubertal children exposed to estrogen were evaluated by means of microarray analysis. The analysis of deregulated genes associated with metabolic disorders allowed us to identify a small group of genes that are expressed in an opposite manner from that of adipocytes treated with BPA. In particular, we found that BPA increases the expression of pro-inflammatory cytokines and the expression ofFABP4andCD36, two genes involved in lipid metabolism. In addition, BPA decreases the expression ofPCSK1, a gene involved in insulin production. These results indicate that exposure to BPA may be an important risk factor for developing metabolic disorders that are involved in childhood metabolism dysregulation.


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