Screening of some anti-androgenic endocrine disruptors using a recombinant cell-based in vitro bioassay

Roy, Partha; Salminen, Heli; Koskimies, Pasi; Simola, Janne; Smeds, Annika; Saukko, Pekka; Huhtaniemi, Ilpo

doi:10.1016/j.jsbmb.2003.11.005

Cited by 89 publications

(74 citation statements)

References 38 publications

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“…Because of their ability to transactivate the AR in vitro, 5a-dihydrotestosterone (DHT) and 17a-methyltestosterone (MT) have been confirmed as strong xenoandrogens (Hossain et al 2008). Using in vitro bioassays, a range of compounds such as prochloraz, fenarimol, and flutamide have also been shown to be AR antagonists (Sohoni and Sumpter 1998;Roy et al 2004).…”

Section: Estrogen-and Androgen-like Endocrine Disrupting Contaminantsmentioning

confidence: 99%

The effects of estrogenic and androgenic endocrine disruptors on the immune system of fish: a review

2011

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During the last decade, a number of studies have shown that, in addition to their classically described reproductive function, estrogens and androgens also regulate the immune system in teleosts. Today, several molecules are known to interfere with the sex-steroid signaling. These chemicals are often referred to as endocrine disrupting contaminants (EDCs). We review the growing evidence that these compounds interfere with the fish immune system. These studies encompass a broad range of approaches from field studies to those at the molecular level. This integrative overview improves our understanding of the various endocrine-disrupting processes triggered by these chemicals. Furthermore, the research also explains why fish that have been exposed to EDCs are more sensitive to pathogens during gametogenesis. In this review, we first discuss the primary actions of sex-steroid-like endocrine disruptors in fish and the specificity of the fish immune system in comparison to mammals. Then, we review the known interactions between the immune system and EDCs and interpret the primary effects of sex steroids (estrogens and androgens) and their related endocrine disruptors on immune modulation. The recent literature suggests that immune parameters may be used as biomarkers of contamination by EDCs. However, caution should be used in the assessment of such immunotoxicity. In particular, more attention should be paid to the specificity of these biomarkers, the external/internal factors influencing the response, and the transduction pathways induced by these molecules in fish. The use of the well-known mammalian models provides a useful guide for future research in fish.

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Section: Estrogen-and Androgen-like Endocrine Disrupting Contaminantsmentioning

confidence: 99%

The effects of estrogenic and androgenic endocrine disruptors on the immune system of fish: a review

2011

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“…The weak antagonistic activity of procymidone and NP is in agreement with previous reports in which both compounds showed very weak antagonist effects. [8,9] The difference in the K i values obtained by a binding assay and by the present method is most probably due to the fact that a binding assay represents the direct binding event of a ligand with a purified receptor, whereas the present FRETbased method represents the ability of a ligand, after penetrating through the cell membrane, to induce a distinct conformational change in the receptor that promotes/inhibits the interaction of the receptor with the coactivator. The receptor/coactivator interaction is a critical step for the transcription activation of the receptor.…”

mentioning

confidence: 95%

“…[6] These chemicals mimic or block the natural androgen activities in the living body by binding with the AR. In vitro receptor binding [7,8] and reporter-gene assays [9][10][11] are used routinely to evaluate interactions of ligands with the AR. For a receptorbinding assay, a large amount of purified receptor protein is required and it is not possible to distinguish between the agonistic and antagonistic effects of a ligand.…”

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confidence: 99%

“…[5,10] No change in the CFP/ YFP ratio was observed (Figure 6 a). Flutamide and other AR antagonists [9,10,29] such as genistein (Gen, a phytoestrogen), bisphenol-A (Bis-A, an environmental endocrine disruptor (ED)), procymidone (a fungicide and an ED), and nonylphenol (NP, an environmental ED) were each added to cells at concentrations of 0.01-100 mm to determine their ability to induce FRET. No increase in FRET was observed with these chemicals (data not shown).…”

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confidence: 99%

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A Fluorescent Indicator To Visualize Activities of the Androgen Receptor Ligands in Single Living Cells

et al. 2006

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“…24) A highly sensitive and simple ligand binding assay for membrane receptors, especially GPCRs, had always been challenging. Here, this assay constructed by us was based on HEK293 cells that were co-transfected with the human NMU2R gene and an integrated copy of a luciferase reporter gene driven by a SV40 promoter under the control of a 3×MRE, 3×CRE, and 3×SRE enhancer elements (NMU2R/pcDNA3.1(+)-3×CRE/3×MRE/ SRE-LUC/pGL3).…”

Section: Discussionmentioning

confidence: 99%

<i>p</i>-Synephrine: A Novel Agonist for Neuromedin U2 Receptor

Zheng

Guo

Wang

et al. 2014

Biological & Pharmaceutical Bulletin

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In the brain, Neuromedin U2 receptor (NMU2R) is prominent in the hypothalamic regions and is known to be associated with regulation of several important physiological functions, including food intake, energy balance, stress response, and nociception. In this article, by random screening of compounds using the model of high-throughput screening for NMU2R stable expression, NMU2R negative and NMU2R short hairpin RNA (shRNA) knockdown HEK293 cell lines, for the first time, we discovered that p-synephrine, which is the primary protoalkaloid in Citrus aurantium (bitter orange) and is widely used in weight loss and weight management products, is a highly potent and selective NMU2R agonist. In NMU2R activating ability experiments, p-synephrine was found binding to NMU2R with high efficacy and potency; the efficacy, 50% of the maximum possible effect (EC 50 ) and potency values were determined to be 7.207, 6.604 and 0.227 µmol/L for the NMU2R, respectively. Our researches have important theoretical value for elucidating the mechanisms of p-synephrine in body weight and energy balance regulation. These data provide further evidence for widespread roles for p-synephrine and its receptors in the brain.

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Screening of some anti-androgenic endocrine disruptors using a recombinant cell-based in vitro bioassay

Cited by 89 publications

References 38 publications

The effects of estrogenic and androgenic endocrine disruptors on the immune system of fish: a review

The effects of estrogenic and androgenic endocrine disruptors on the immune system of fish: a review

A Fluorescent Indicator To Visualize Activities of the Androgen Receptor Ligands in Single Living Cells

<i>p</i>-Synephrine: A Novel Agonist for Neuromedin U2 Receptor

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