Anti-estrogenic activity of fifty chemicals evaluated by in vitro assays

Jung, Joohee; Ishida, Kunie; Nishihara, Tsutomu

doi:10.1016/j.lfs.2003.10.030

Cited by 60 publications

(41 citation statements)

References 18 publications

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“…with these steroid receptors were approximate equivalent. These results may provide molecular evidences for previously reported estrogenic, anti-estrogenic, anti-androgenic activity of PCP in vitro (Suzuki et al, 2001;Jung et al, 2004;Orton et al, 2009;Li et al, 2008aLi et al, , 2008bLi et al, , 2010b and in vivo (Zha et al, 2006;Zhang et al, 2008a). Moreover, molecular docking results showed that PCP could not interact with any of the agonistic or antagonistic conformations of CYPs.…”

Section: Discussionsupporting

confidence: 75%

“…PCP has been demonstrated to display estrogenic, anti-estrogenic, antiandrogenic, thyroid receptor and retinoid X receptor antagonistic activity in vitro (Suzuki et al, 2001;Jung et al, 2004;Orton et al, 2009;Li et al, 2008aLi et al, , 2008bLi et al, , 2010b and disturb the hypothalamic-pituitary-gonadal (HPG) axis in vivo (Zha et al, 2006;Zhang et al, 2008a). However, the underlying mechanism such as molecular initiating event (MIE) and the following regulating process has not been fully understood.…”

Section: Introductionmentioning

confidence: 99%

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Pentachlorophenol affected both reproductive and interrenal systems: In silico and in vivo evidence

2017

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h i g h l i g h t s g r a p h i c a l a b s t r a c tThe effects of PCP on steroid system were studied by in silico and in vivo assays.In silico results indicated interacting potency with steroid receptors by PCP. PCP caused adverse effects on reproductive and interrenal system in rare minnow. The HPG/I axis of rare minnow showed different response at 14th and 28th day.a r t i c l e i n f o The present study investigated the effects on reproductive and interrenal system by pentachlorophenol (PCP) using in silico and in vivo assays. Molecular docking results indicated interacting potency of PCP with steroid receptors (ERa, ERb, AR, GR) but not Cytochrome P450 enzymes (CYPs). In the in vivo assay, sexually matured rare minnow (Gobiocypris rarus) was exposed to environmental relevant concentrations of PCP (0, 0.5, 5, 50 mg L À1 ). In male fish, 14-d exposure caused up-regulation of mRNA levels of hepatic era, erb, ar, gr, vtg and gonadal era, vtg, ar, dmrt1, providing evidence for agonistic activities for steroid receptors by PCP. The up-regulated mRNA of gnrh, crf, pomc in the brain also indicated feedforward responses of the hypothalamic-pituitary-gonadal/interrenal (HPG/I) axis. However, at 28th d the feed-forward response of the HPG axis seemed eased back and the HPI axis showed negative feedback responses. Corresponding changes including increases of plasma steroid hormones, inhibition of spermatogenesis, and decreased RSI were observed in male fish upon 28-d exposure to PCP. In the females, a transition from feed-forward responses to negative feedbacks of the HPG/I axis was also indicated by the transcriptional profiles at 14th and 28th day. Corresponding changes including increased E2, T and decreased C levels, degenerated ovaries, and decreased GSI and RSI were also observed. Overall, we concluded that PCP could interfere with steroid receptors, evoke responses of HPG/I axis, and finally result in adverse effects on reproductive and interrenal system in rare minnow at environmental relevant concentrations.

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Section: Discussionsupporting

confidence: 75%

Section: Introductionmentioning

confidence: 99%

Pentachlorophenol affected both reproductive and interrenal systems: In silico and in vivo evidence

2017

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“…For example, PCP was shown to be a partial agonist for the estrogen receptor (ER) in the cellular proliferation of MCF-7 cells (Suzuki et al, 2001) and other estrogenic activity, such as induction of vitellogenin (VTG) in the cultured hepatocytes of male channel catfish (Dorsey and Tchounwou, 2004). Alternatively, the results of other studies have indicated that PCP did not exhibit estrogenicity, but rather was shown to be anti-estrogenic in the yeast two-hybrid assay (Jung et al, 2004) and in cultured goldfish hepatocytes . In fish, estrogenic activities (induction of VTG), and reproductive impairment have been reported in male Japanese medaka (Zha et al, 2006), while significantly more testosterone (T) was observed in the serum crucian carp exposed to PCP .…”

Section: Introductionmentioning

confidence: 99%

Modulation of steroidogenic gene expression and hormone synthesis in H295R cells exposed to PCP and TCP

Liu

et al. 2011

Toxicology

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“…While it has been proposed that chemical modification of ER zinc fingers may inhibit the growth of some ER expressing cancers by preventing ER dimerization and transactivation [5,6], it has also been shown that exposure to electrophilic quinones such as those generated during estrogen metabolism can induce tumorigenesis via their redox cycling or direct structural attack of nucleic acids and proteins, including ER [11][12][13][14][15]. Of particular interest, protein-quinone conjugates can theoretically become molecular platforms for continued intracellular quinonehydroquinone cycling, local generation of reactive oxy-gen species (ROS), and chronic propagation of oxidative damage to surrounding macromolecules.…”

mentioning

confidence: 99%

Reactivity of zinc finger cysteines: Chemical modifications within labile zinc fingers in estrogen receptor

Atsriku

Scott

Benz

et al. 2005

J. Am. Soc. Mass Spectrom.

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Estrogen receptor (ER, alpha isoform) is a 67 kDa zinc finger transcription factor that plays a fundamental role in both normal reproductive gland development and breast carcinogenesis, and also represents a critical molecular target for breast cancer therapy. We are investigating the structural consequences of chemical exposures thought to modify essential zinc finger cysteine residues in human ER. The current study employs mass spectrometry to probe ER zinc finger structural changes induced by a redox-reactive vitamin K3 analog, menadione; a commonly used cysteine alkylator, iodoacetic acid; and a thiol alkylating fluorophore, monobromobimane. Although they are slower to react, the sterically bulkier reagents, monobromobimane and menadione, effectively alkylate the most susceptible ER zinc finger cysteine sulfhydryl groups. Menadione arylation results first in Michael addition of the hydroquinone followed by rapid oxidation to the corresponding quinone, evidenced by a 2 Da mass loss per cysteine residue. Mass spectrometric analysis performed under MALDI conditions reveals both hydroquinone and quinone forms of arylated menadione, whereas only the quinone product is detectable under ESI conditions. Tandem mass spectrometry of a synthetic peptide encompassing the C-terminal half of the structurally more labile second zinc finger of ER (ZnF2B) demonstrates that the two nucleophilic thiols in ZnF2B (Cys-237, Cys-240) are not chemically equivalent in their reactivity to bromobimane or menadione, consistent with their unequal positioning near basic amino acids that affect thiol pKa, thereby rendering Cys-240 more reactive than Cys-237. These findings demonstrate important differential susceptibility of ER zinc finger cysteine residues to thiol reactions. (J Am Soc Mass Spectrom

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Anti-estrogenic activity of fifty chemicals evaluated by in vitro assays

Cited by 60 publications

References 18 publications

Pentachlorophenol affected both reproductive and interrenal systems: In silico and in vivo evidence

Pentachlorophenol affected both reproductive and interrenal systems: In silico and in vivo evidence

Modulation of steroidogenic gene expression and hormone synthesis in H295R cells exposed to PCP and TCP

Reactivity of zinc finger cysteines: Chemical modifications within labile zinc fingers in estrogen receptor

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