Use of Reporter Genes to Analyze Estrogen Response: The Transgenic Zebrafish Model

Gorelick, Daniel A.; Pinto, Caroline; Hao, Ruixin; Bondesson, Maria

doi:10.1007/978-1-4939-3127-9_24

Cited by 7 publications

(5 citation statements)

References 15 publications

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“…To investigate the antagonist activity of BPC in vivo, we co-treated zebrafish embryos with the estrogenic ligand EE2, which is more stable than E2 in vivo, or 16α-LE2 in combination with BPC (Figure 3 and Figure 4). Treatment with 100 pM EE2 induced GFP expression both in the heart and liver of the embryos, in accordance with its pan-agonist ER activity ( Figure 3C) (Pinto et al, 2014;Gorelick et al, 2016). The pure antagonist ICI 182,780 completely blocked both heart and liver GFP expression ( Figure 3E).…”

Section: Activation Of Estrogen Signaling By Bisphenols In Tg Ere-gfpsupporting

confidence: 66%

“…For instance, in transgenic zebrafish model containing five EREs (Tg(5×ERE:GFP)) (Gorelick and Halpern, 2011), the GFP expression is clearly detected in tissues expressing the estrogen receptors. Thus, compounds with in vitro selectivity for zfERα and zfERβs induce expression of the fluorescent protein in the heart and liver, respectively (Gorelick et al, 2016). For example, PPT specifically activates the zfERβs receptors in vitro and induces GFP expression only in the liver of zebrafish larvae, whereas the pan-agonist 17α-ethinylestradiol induces GFP in both heart and liver (Gorelick and Halpern, 2011;Pinto et al, 2014;Gorelick et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

“…Thus, compounds with in vitro selectivity for zfERα and zfERβs induce expression of the fluorescent protein in the heart and liver, respectively (Gorelick et al, 2016). For example, PPT specifically activates the zfERβs receptors in vitro and induces GFP expression only in the liver of zebrafish larvae, whereas the pan-agonist 17α-ethinylestradiol induces GFP in both heart and liver (Gorelick and Halpern, 2011;Pinto et al, 2014;Gorelick et al, 2016). Another reporter fish model, the transgenic cyp19a1b-GFP zebrafish, expresses GFP under the control of the ER-regulated cyp19a1b (brain aromatase) gene in radial glial cells in the brain (Tong et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

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Differential activity of BPA, BPAF and BPC on zebrafish estrogen receptors in vitro and in vivo

Pinto

Hao

Grimaldi

et al. 2019

Toxicology and Applied Pharmacology

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The high volume production compound bisphenol A (BPA) is of environmental concern largely because of its estrogenic activity. Consequently, BPA analogues have been synthesized to be considered as replacement molecules for BPA. These analogues need to be thoroughly evaluated for their estrogenic activity. Here, we combined mechanism zebrafish-based assays to examine estrogenic and anti-estrogenic activities of BPA and two of its analogues, bisphenol AF (BPAF) and bisphenol C (BPC) in vitro and in vivo. In vitro reporter cell lines were used to investigate agonistic and antagonistic effects of the three bisphenols on the three zebrafish estrogen receptors. The transgenic Tg(5×ERE:GFP) and Cyp19a1b-GFP zebrafish lines were then used to analyze estrogenic and anti-estrogenic responses of the three bisphenols in vivo. BPA, BPAF and BPC were agonists with different potencies for the three zebrafish estrogen receptors in vitro. The

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Section: Activation Of Estrogen Signaling By Bisphenols In Tg Ere-gfpsupporting

confidence: 66%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Differential activity of BPA, BPAF and BPC on zebrafish estrogen receptors in vitro and in vivo

Pinto

Hao

Grimaldi

et al. 2019

Toxicology and Applied Pharmacology

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“…A fully functional stress axis leading to the release of cortisol by the interrenal gland, the fish counterpart to the mammalian adrenal gland [ 53 ], is present at four to five days of development [ 32 , 38 , 76 ]. Several zebrafish mutants [ 19 , 23 , 33 , 60 ] and transgenic reporter lines [ 6 , 8 , 24 , [28] , [29] , [30] , 37 , 44 , 63 , 75 , 76 ] of steroid hormone synthesis and action have been established. They allow for comprehensive analysis of in vivo processes and for high-throughput compound screenings to identify novel drug targets.…”

Section: Introductionmentioning

confidence: 99%

Glucocorticoid deficiency causes transcriptional and post-transcriptional reprogramming of glutamine metabolism

Weger

Görling

et al. 2018

EBioMedicine

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BackgroundDeficient glucocorticoid biosynthesis leading to adrenal insufficiency is life-threatening and is associated with significant co-morbidities. The affected pathways underlying the pathophysiology of co-morbidities due to glucocorticoid deficiency remain poorly understood and require further investigation.MethodsTo explore the pathophysiological processes related to glucocorticoid deficiency, we have performed global transcriptional, post-transcriptional and metabolic profiling of a cortisol-deficient zebrafish mutant with a disrupted ferredoxin (fdx1b) system.Findingsfdx1b−/− mutants show pervasive reprogramming of metabolism, in particular of glutamine-dependent pathways such as glutathione metabolism, and exhibit changes of oxidative stress markers. The glucocorticoid-dependent post-transcriptional regulation of key enzymes involved in de novo purine synthesis was also affected in this mutant. Moreover, fdx1b−/− mutants exhibit crucial features of primary adrenal insufficiency, and mirror metabolic changes detected in primary adrenal insufficiency patients.InterpretationOur study provides a detailed map of metabolic changes induced by glucocorticoid deficiency as a consequence of a disrupted ferredoxin system in an animal model of adrenal insufficiency. This improved pathophysiological understanding of global glucocorticoid deficiency informs on more targeted translational studies in humans suffering from conditions associated with glucocorticoid deficiency.FundMarie Curie Intra-European Fellowships for Career Development, HGF-programme BIFTM, Deutsche Forschungsgemeinschaft, BBSRC.

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“…Two common zebrafish transgenic reporters that are used for the detection of estrogen receptor signaling are the Tg(5xERE:GFP) (Gorelick & Halpern, 2011; Gorelick et al, 2016) and Tg(cyp19a1b:GFP) (Cano-Nicolau et al, 2016; Sonavane et al, 2016) zebrafish lines. These lines respond to a range of estrogenic compounds at different doses.…”

Section: Zebrafish: Testing the Waters For Toxicantsmentioning

confidence: 99%

Zebrafish in Toxicology and Environmental Health

Bambino

Chu

2017

Current Topics in Developmental Biology

290

152

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As manufacturing processes and development of new synthetic compounds increase to keep pace with the expanding global demand, environmental health, and the effects of toxicant exposure are emerging as critical public health concerns. Additionally, chemicals that naturally occur in the environment, such as metals, have profound effects on human and animal health. Many of these compounds are in the news: lead, arsenic, and endocrine disruptors such as bisphenol A have all been widely publicized as causing disease or damage to humans and wildlife in recent years. Despite the widespread appreciation that environmental toxins can be harmful, there is limited understanding of how many toxins cause disease. Zebrafish are at the forefront of toxicology research; this system has been widely used as a tool to detect toxins in water samples and to investigate the mechanisms of action of environmental toxins and their related diseases. The benefits of zebrafish for studying vertebrate development are equally useful for studying teratogens. Here, we review how zebrafish are being used both to detect the presence of some toxins as well as to identify how environmental exposures affect human health and disease. We focus on areas where zebrafish have been most effectively used in ecotoxicology and in environmental health, including investigation of exposures to endocrine disruptors, industrial waste byproducts, and arsenic.

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Use of Reporter Genes to Analyze Estrogen Response: The Transgenic Zebrafish Model

Cited by 7 publications

References 15 publications

Differential activity of BPA, BPAF and BPC on zebrafish estrogen receptors in vitro and in vivo

Differential activity of BPA, BPAF and BPC on zebrafish estrogen receptors in vitro and in vivo

Glucocorticoid deficiency causes transcriptional and post-transcriptional reprogramming of glutamine metabolism

Zebrafish in Toxicology and Environmental Health

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