In vitro exposure to xenoestrogens induces growth hormone transcription and release via estrogen receptor-dependent pathways in rat pituitary GH3 cells

Dang, Hoang Vu; Nguyen, Thi Hoa; Lee, Geun‐Shik; Choi, Kyung‐Chul; Jeung, Eui‐Bae

doi:10.1016/j.steroids.2009.03.002

Cited by 32 publications

(17 citation statements)

References 62 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It has been reported that EED as well as E 2 mainly exert their estrogenic effects through classic ER-dependent pathway (30)(31)(32). ER· and ERß, encoded by ESR1 and ESR2 gene, respectively, are the main ER subtypes (39).…”

Section: Discussionmentioning

confidence: 99%

“…way is known to be involved in the estrogenic activities of environmental endocrine disruptors and estrogen (30)(31)(32). Therefore, ER antagonist ICI182,780 was applied to determine whether ER-dependent pathway was also involved in the process of DEHP, BPA or E 2 regulating cellular motility or invasiveness.…”

Section: Ici182780 and Ly294002 Treatments Both Abolished The Effectmentioning

confidence: 99%

See 1 more Smart Citation

Environmental endocrine disruptors promote invasion and metastasis of SK-N-SH human neuroblastoma cells

Xiao¹

2009

Oncol Rep

View full text Add to dashboard Cite

Abstract. Neuroblastoma (NB) is the most common pediatric extracranial cancer. Metastasis is the main cause of mortality in NB patients. Currently, little is known about the risk factors and their mechanisms that cause metastasis. Environmental endocrine disruptors (EED) are recently identified risk factors associated with various human diseases including malignant tumors. Our previous studies have implicated the role of di(2-ethylhexyl) phthalate (DEHP) and bisphenol A (BPA), two of the most common EED, in neuroblastoma cell proliferation. Here, we further investigated the effects of DEHP, BPA as well as 17ß-estradiol (E 2 ) on the invasion and metastasis of human neuroblastoma SK-N-SH cells in vitro. SK-N-SH cells expressed estrogen receptor (ER)-ß, matrix metalloproteinases-2 (MMP-2), MMP-9 and tissue inhibitor of matrix metalloproteinase-2 (TIMP-2) at readily detectable levels. 50 μM DEHP, 0.1 μM BPA and 10 μM E 2 exposure all resulted in enhanced motility and invasiveness of SK-N-SH cells (P<0.001), elevated expression of MMP-2 and MMP-9, and decreased expression of TIMP-2 (P<0.01). Furthermore, phosphorylation of Akt (Ser473) was also induced following the exposure (P<0.01). Importantly, both ER antagonist ICI182,780 and phosphoinositide 3-kinase (PI3K) specific inhibitor LY294002 significantly inhibited the DEHP, BPA, or E 2 -induced cell migration and invasion, as well as the disregulation of MMP-2, MMP-9 and TIMP-2 expression. ICI182,780 may have worked through abolishing Akt (Ser473) phosphorylation. In conclusion, DEHP, BPA, and E 2 potently promote invasion and metastasis of neuroblastoma cells through overexpression of MMP-2 and MMP-9 as well as downregulation of TIMP-2. ER-dependent pathway and PI3K/Akt pathway are involved, which may become potential therapeutic targets for neuroblastoma treatment.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Ici182780 and Ly294002 Treatments Both Abolished The Effectmentioning

confidence: 99%

Environmental endocrine disruptors promote invasion and metastasis of SK-N-SH human neuroblastoma cells

Xiao¹

2009

Oncol Rep

View full text Add to dashboard Cite

show abstract

“…Additionally BPA at micromolar concentrations can interact with the function and protein binding of triiodothyronine (Okada et al, 2007). Weak endocrine-disrupting effects involve interactions with growth hormone expression (Dang et al, 2009). …”

Section: Effects On Receptors and Hormone Homeostasismentioning

confidence: 99%

Scientific Opinion on Bisphenol A: evaluation of a study investigating its neurodevelopmental toxicity, review of recent scientific literature on its toxicity and advice on the Danish risk assessment of Bisphenol A

Flavourings¹

2010

EFSA Journal

View full text Add to dashboard Cite

Bisphenol A (BPA) is used in the manufacture of plastics, to produce reusable drinking bottles, infant feeding bottles and other food storage containers. EFSA was asked to evaluate a dietary developmental neurotoxicity study in rats (Stump, 2009) and recent scientific literature (2007)(2008)(2009)(2010) in terms of relevance for the risk assessment of BPA. The impact of these studies on the current Tolerable Daily Intake (TDI) of 0.05 mg BPA/kg body weight (b.w.)/day as set by EFSA in 2006 was assessed. Advice on the Danish risk assessment underlying the Danish ban of BPA in food contact materials for infants aged 0-3 years is included. Overall, based on this comprehensive evaluation of recent toxicity data, the Panel on food contact materials, enzymes, flavourings and processing aids (CEF) concluded that no new study could be identified, which would call for a revision of the current TDI. This TDI is based on the No-Observed-Adverse-Effect-Level (NOAEL) of 5 mg/kg b.w./day from a multi-generation reproductive toxicity study in rats, and the application of an uncertainty factor of 100. This factor is regarded as conservative based on all information on BPA toxicokinetics. The Panel noted that some studies conducted on developing animals have suggested other BPA-related effects of possible toxicological relevance, in particular biochemical changes in brain, immune-modulatory effects and enhanced susceptibility to breast tumours. These studies had several shortcomings. At present the relevance of these findings for human health cannot be assessed. Should any new relevant data become available in the future, the Panel will reconsider this opinion. A minority opinion is expressed by a Panel member and presented in an Annex to this opinion. © European Food Safety Authority, 2010 KEY WORDSBisphenol A, BPA, CAS No. 00080-05-7, developmental toxicity, neurobehaviour, low dose effects. In order to provide a global view on the risk assessment of Bisphenol A, the CEF Panel decided to address the three mandates as given above in a single opinion and postponed the adoption of this comprehensive document to 23 rd September 2010.The three different questions raised by the Commission are dealt with in three different parts (PARTS I to III) of the opinion. PART IV presents an overview of the conclusions from PARTS I to III, together with an overall conclusion. PART IThe GLP compliant study by Stump (2009) was performed according to OECD guideline 426 to address any uncertainty regarding potential neurodevelopmental effects of BPA. BPA was administered daily in the diet at concentrations of 0, 0.15, 1.5, 75, 750, and 2250 mg/kg feed to female Sprague-Dawley rats from gestational day (GD) 0 to postnatal day (PND) 21. The relative estimated intakes (in mg/kg b.w./day) were 0, 0.01, 0.12, 5.85, 56.4 and 164 during gestation and 0, 0.03, 0.25, 13.1, 129 and 410 during lactation. The CEF Panel considers this treatment schedule as relevant to human exposure in utero and via either breastfeeding or infant bottle feeding (in this...

show abstract

“…These adverse effects of EDCs consequently result in human health problems associated with reproduction, development, and the neurologic and immune systems (3). Most natural and synthetic EDCs tend to have estrogenic activities and structures similar to that of estrogen such as 17β-estradiol (E2); thus, they induce estrogen-mediated responses by binding to estrogen receptors (ERs) (4). ERs are members of the nuclear receptor family and play a key role as transcription factors (TFs) in gene expression (5).…”

Section: Introductionmentioning

confidence: 99%

Treatment with bisphenol A and methoxychlor results in the growth of human breast cancer cells and alteration of the expression of cell cycle-related genes, cyclin D1 and p21, via an estrogen receptor-dependent signaling pathway

Choi

2012

Int J Mol Med

Self Cite

View full text Add to dashboard Cite

Abstract. Various endocrine disrupting chemicals (EDCs) are exogenous compounds found in the environment and have the potential to interfere with the endocrine system and hormonal regulation. Among EDCs, bisphenol A (BPA) and 1,1,1-trichloro-2,2-bis(4-methoxyphenol)-ethane [methoxychlor (MXC)] have estrogenic activity resulting in a variety of dysfunctions in the E2-mediated response by binding to estrogen receptors (ERs), causing human health problems such as abnormal reproduction and carcinogenesis. In this study, we investigated the effects of BPA and MXC on cell proliferation facilitated by ER signaling in human breast cancer cells. MCF-7 cells are known to be ERα-positive and to be a highly E2-responsive cancer cell line; these cells are, therefore, a useful in vitro model for detecting estrogenic activity in response to EDCs. We evaluated cancer cell proliferation following BPA and MXC treatment using an MTT assay. We analyzed alterations in the expression of genes associated with the cell cycle in MCF-7 cells by semi-quantitative reverse-transcription PCR following treatment with BPA or MXC compared to EtOH. To determine whether BPA and MXC stimulate cancer cell growth though ER signaling, we co-treated the cells with agonists (propyl pyrazoletriol, PPT; and diarylpropionitrile, DPN) or an antagonist (ICI 182,780) of ER signaling and reduced ERα gene expression via siRNA in MCF-7 cells before treatment with EDCs. These studies confirmed the carcinogenicity of EDCs in vitro. As a result, BPA and MXC induced the cancer cell proliferation by the upregulation of genes that promote the cell cycle and the downregulation of anti-proliferative genes, especially ones affecting the G1/S transition via ERα signaling. These collective results confirm the carcinogenicity of these EDCs in vitro. Further studies are required to determine whether EDCs promote carcinogenesis in vivo.

show abstract

In vitro exposure to xenoestrogens induces growth hormone transcription and release via estrogen receptor-dependent pathways in rat pituitary GH3 cells

Cited by 32 publications

References 62 publications

Environmental endocrine disruptors promote invasion and metastasis of SK-N-SH human neuroblastoma cells

Environmental endocrine disruptors promote invasion and metastasis of SK-N-SH human neuroblastoma cells

Scientific Opinion on Bisphenol A: evaluation of a study investigating its neurodevelopmental toxicity, review of recent scientific literature on its toxicity and advice on the Danish risk assessment of Bisphenol A

Treatment with bisphenol A and methoxychlor results in the growth of human breast cancer cells and alteration of the expression of cell cycle-related genes, cyclin D1 and p21, via an estrogen receptor-dependent signaling pathway

Contact Info

Product

Resources

About