Identification and Characterization of Androgen-Responsive Genes in Zebrafish Embryos
Responsive genes for fish embryos have been identified so far for some endocrine pathways but not for androgens. Using transcriptome analysis and multiple concentration–response modeling, we identified putative androgen-responsive genes in zebrafish embryos exposed to 0.05–5000 nM 11-ketotestosteron...
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Veröffentlicht in: | Environmental science & technology 2015-10, Vol.49 (19), p.11789-11798 |
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description | Responsive genes for fish embryos have been identified so far for some endocrine pathways but not for androgens. Using transcriptome analysis and multiple concentration–response modeling, we identified putative androgen-responsive genes in zebrafish embryos exposed to 0.05–5000 nM 11-ketotestosterone for 24 h. Four selected genes with sigmoidal concentration-dependent expression profiles (EC50 = 6.5–30.0 nM) were characterized in detail. The expression of cyp2k22 and slco1f4 was demonstrated in the pronephros; lipca was detected in the liver, and sult2st3 was found in the olfactory organs and choroid plexus. Their expression domains, the function of human orthologs, and a pathway analysis suggested a role of these genes in the metabolism of hormones. Hence, it was hypothesized that they were induced to compensate for elevated hormone levels. The induction of sult2st3 and cyp2k22 by 11-ketotestosterone was repressed by co-exposure to the androgen receptor antagonist nilutamide supporting a potential androgen receptor mediated regulation. Sensitivity (expressed as EC50 values) of sult2st3 and cyp2k22 gene expression induction after exposure to other steroidal hormones (11-ketotestosterone ∼ testosterone > progesterone > cortisol > ethinylestradiol) correlated with their known binding affinities to zebrafish androgen receptor. Hence, these genes might represent potential markers for screening of androgenic compounds in the zebrafish embryo. |
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Using transcriptome analysis and multiple concentration–response modeling, we identified putative androgen-responsive genes in zebrafish embryos exposed to 0.05–5000 nM 11-ketotestosterone for 24 h. Four selected genes with sigmoidal concentration-dependent expression profiles (EC50 = 6.5–30.0 nM) were characterized in detail. The expression of cyp2k22 and slco1f4 was demonstrated in the pronephros; lipca was detected in the liver, and sult2st3 was found in the olfactory organs and choroid plexus. Their expression domains, the function of human orthologs, and a pathway analysis suggested a role of these genes in the metabolism of hormones. Hence, it was hypothesized that they were induced to compensate for elevated hormone levels. The induction of sult2st3 and cyp2k22 by 11-ketotestosterone was repressed by co-exposure to the androgen receptor antagonist nilutamide supporting a potential androgen receptor mediated regulation. Sensitivity (expressed as EC50 values) of sult2st3 and cyp2k22 gene expression induction after exposure to other steroidal hormones (11-ketotestosterone ∼ testosterone > progesterone > cortisol > ethinylestradiol) correlated with their known binding affinities to zebrafish androgen receptor. Hence, these genes might represent potential markers for screening of androgenic compounds in the zebrafish embryo.</description><identifier>ISSN: 0013-936X</identifier><identifier>EISSN: 1520-5851</identifier><identifier>DOI: 10.1021/acs.est.5b01034</identifier><identifier>PMID: 26308493</identifier><identifier>CODEN: ESTHAG</identifier><language>eng</language><publisher>United States: American Chemical Society</publisher><subject>Androgen Antagonists - pharmacology ; Androgens ; Androgens - genetics ; Androgens - metabolism ; Animals ; Danio rerio ; Embryo, Nonmammalian - drug effects ; Embryos ; Environmental science ; Ethinyl Estradiol - pharmacology ; Female ; Freshwater ; Gene expression ; Gene Expression - drug effects ; Gene Expression Profiling ; Gene Expression Regulation, Developmental - drug effects ; Genes ; Hormones ; Humans ; Imidazolidines - pharmacology ; Receptors, Androgen - genetics ; Testosterone - analogs & derivatives ; Testosterone - pharmacology ; Zebrafish ; Zebrafish - embryology ; Zebrafish - genetics</subject><ispartof>Environmental science & technology, 2015-10, Vol.49 (19), p.11789-11798</ispartof><rights>Copyright © 2015 American Chemical Society</rights><rights>Copyright American Chemical Society Oct 6, 2015</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a460t-f903f6712ea4d6729baff6cc35c0bb429a9d6c32e2cd15bb17506902c62b05e03</citedby><cites>FETCH-LOGICAL-a460t-f903f6712ea4d6729baff6cc35c0bb429a9d6c32e2cd15bb17506902c62b05e03</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://pubs.acs.org/doi/pdf/10.1021/acs.est.5b01034$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/acs.est.5b01034$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>314,780,784,2765,27076,27924,27925,56738,56788</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26308493$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Fetter, Eva</creatorcontrib><creatorcontrib>Smetanová, Soňa</creatorcontrib><creatorcontrib>Baldauf, Lisa</creatorcontrib><creatorcontrib>Lidzba, Annegret</creatorcontrib><creatorcontrib>Altenburger, Rolf</creatorcontrib><creatorcontrib>Schüttler, Andreas</creatorcontrib><creatorcontrib>Scholz, Stefan</creatorcontrib><title>Identification and Characterization of Androgen-Responsive Genes in Zebrafish Embryos</title><title>Environmental science & technology</title><addtitle>Environ. Sci. Technol</addtitle><description>Responsive genes for fish embryos have been identified so far for some endocrine pathways but not for androgens. Using transcriptome analysis and multiple concentration–response modeling, we identified putative androgen-responsive genes in zebrafish embryos exposed to 0.05–5000 nM 11-ketotestosterone for 24 h. Four selected genes with sigmoidal concentration-dependent expression profiles (EC50 = 6.5–30.0 nM) were characterized in detail. The expression of cyp2k22 and slco1f4 was demonstrated in the pronephros; lipca was detected in the liver, and sult2st3 was found in the olfactory organs and choroid plexus. Their expression domains, the function of human orthologs, and a pathway analysis suggested a role of these genes in the metabolism of hormones. Hence, it was hypothesized that they were induced to compensate for elevated hormone levels. The induction of sult2st3 and cyp2k22 by 11-ketotestosterone was repressed by co-exposure to the androgen receptor antagonist nilutamide supporting a potential androgen receptor mediated regulation. Sensitivity (expressed as EC50 values) of sult2st3 and cyp2k22 gene expression induction after exposure to other steroidal hormones (11-ketotestosterone ∼ testosterone > progesterone > cortisol > ethinylestradiol) correlated with their known binding affinities to zebrafish androgen receptor. Hence, these genes might represent potential markers for screening of androgenic compounds in the zebrafish embryo.</description><subject>Androgen Antagonists - pharmacology</subject><subject>Androgens</subject><subject>Androgens - genetics</subject><subject>Androgens - metabolism</subject><subject>Animals</subject><subject>Danio rerio</subject><subject>Embryo, Nonmammalian - drug effects</subject><subject>Embryos</subject><subject>Environmental science</subject><subject>Ethinyl Estradiol - pharmacology</subject><subject>Female</subject><subject>Freshwater</subject><subject>Gene expression</subject><subject>Gene Expression - drug effects</subject><subject>Gene Expression Profiling</subject><subject>Gene Expression Regulation, Developmental - drug effects</subject><subject>Genes</subject><subject>Hormones</subject><subject>Humans</subject><subject>Imidazolidines - pharmacology</subject><subject>Receptors, Androgen - genetics</subject><subject>Testosterone - analogs & derivatives</subject><subject>Testosterone - pharmacology</subject><subject>Zebrafish</subject><subject>Zebrafish - embryology</subject><subject>Zebrafish - genetics</subject><issn>0013-936X</issn><issn>1520-5851</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kEFrGzEQRkVoqR2n59zKQi-FsPZIWmmtYzBuEjAUSgMll0XSjmIZW3KldSD59d3FTgKFngaG930zPEIuKUwpMDrTNk8xd1NhgAKvzsiYCgalmAv6gYwBKC8Vl79H5DznDQAwDvNPZMRkPyvFx-T-rsXQeeet7nwMhQ5tsVjrpG2Hyb8cl9EV16FN8RFD-RPzPobsn7C4wYC58KF4QJO083ldLHcmPcd8QT46vc34-TQn5P778tfitlz9uLlbXK9KXUnoSqeAO1lThrpqZc2U0c5Ja7mwYEzFlFattJwhsy0VxtBagFTArGQGBAKfkG_H3n2Kfw69iGbns8XtVgeMh9zQmtWynkte9-jXf9BNPKTQfzdQVFVCVUPh7EjZFHNO6Jp98judnhsKzWC86Y03Q_pkvE98OfUezA7bN_5VcQ9cHYEh-X7zP3V_AW-Yi7s</recordid><startdate>20151006</startdate><enddate>20151006</enddate><creator>Fetter, Eva</creator><creator>Smetanová, Soňa</creator><creator>Baldauf, Lisa</creator><creator>Lidzba, Annegret</creator><creator>Altenburger, Rolf</creator><creator>Schüttler, Andreas</creator><creator>Scholz, Stefan</creator><general>American Chemical Society</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QO</scope><scope>7ST</scope><scope>7T7</scope><scope>7U7</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>P64</scope><scope>SOI</scope><scope>F1W</scope><scope>H95</scope><scope>L.G</scope><scope>RC3</scope></search><sort><creationdate>20151006</creationdate><title>Identification and Characterization of Androgen-Responsive Genes in Zebrafish Embryos</title><author>Fetter, Eva ; Smetanová, Soňa ; Baldauf, Lisa ; Lidzba, Annegret ; Altenburger, Rolf ; Schüttler, Andreas ; Scholz, Stefan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a460t-f903f6712ea4d6729baff6cc35c0bb429a9d6c32e2cd15bb17506902c62b05e03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Androgen Antagonists - pharmacology</topic><topic>Androgens</topic><topic>Androgens - genetics</topic><topic>Androgens - metabolism</topic><topic>Animals</topic><topic>Danio rerio</topic><topic>Embryo, Nonmammalian - drug effects</topic><topic>Embryos</topic><topic>Environmental science</topic><topic>Ethinyl Estradiol - pharmacology</topic><topic>Female</topic><topic>Freshwater</topic><topic>Gene expression</topic><topic>Gene Expression - drug effects</topic><topic>Gene Expression Profiling</topic><topic>Gene Expression Regulation, Developmental - drug effects</topic><topic>Genes</topic><topic>Hormones</topic><topic>Humans</topic><topic>Imidazolidines - pharmacology</topic><topic>Receptors, Androgen - genetics</topic><topic>Testosterone - analogs & derivatives</topic><topic>Testosterone - pharmacology</topic><topic>Zebrafish</topic><topic>Zebrafish - embryology</topic><topic>Zebrafish - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Fetter, Eva</creatorcontrib><creatorcontrib>Smetanová, Soňa</creatorcontrib><creatorcontrib>Baldauf, Lisa</creatorcontrib><creatorcontrib>Lidzba, Annegret</creatorcontrib><creatorcontrib>Altenburger, Rolf</creatorcontrib><creatorcontrib>Schüttler, Andreas</creatorcontrib><creatorcontrib>Scholz, Stefan</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Environment Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Toxicology Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environment Abstracts</collection><collection>ASFA: Aquatic Sciences and Fisheries Abstracts</collection><collection>Aquatic Science & Fisheries Abstracts (ASFA) 1: Biological Sciences & Living Resources</collection><collection>Aquatic Science & Fisheries Abstracts (ASFA) Professional</collection><collection>Genetics Abstracts</collection><jtitle>Environmental science & technology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Fetter, Eva</au><au>Smetanová, Soňa</au><au>Baldauf, Lisa</au><au>Lidzba, Annegret</au><au>Altenburger, Rolf</au><au>Schüttler, Andreas</au><au>Scholz, Stefan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Identification and Characterization of Androgen-Responsive Genes in Zebrafish Embryos</atitle><jtitle>Environmental science & technology</jtitle><addtitle>Environ. Sci. Technol</addtitle><date>2015-10-06</date><risdate>2015</risdate><volume>49</volume><issue>19</issue><spage>11789</spage><epage>11798</epage><pages>11789-11798</pages><issn>0013-936X</issn><eissn>1520-5851</eissn><coden>ESTHAG</coden><abstract>Responsive genes for fish embryos have been identified so far for some endocrine pathways but not for androgens. Using transcriptome analysis and multiple concentration–response modeling, we identified putative androgen-responsive genes in zebrafish embryos exposed to 0.05–5000 nM 11-ketotestosterone for 24 h. Four selected genes with sigmoidal concentration-dependent expression profiles (EC50 = 6.5–30.0 nM) were characterized in detail. The expression of cyp2k22 and slco1f4 was demonstrated in the pronephros; lipca was detected in the liver, and sult2st3 was found in the olfactory organs and choroid plexus. Their expression domains, the function of human orthologs, and a pathway analysis suggested a role of these genes in the metabolism of hormones. Hence, it was hypothesized that they were induced to compensate for elevated hormone levels. The induction of sult2st3 and cyp2k22 by 11-ketotestosterone was repressed by co-exposure to the androgen receptor antagonist nilutamide supporting a potential androgen receptor mediated regulation. Sensitivity (expressed as EC50 values) of sult2st3 and cyp2k22 gene expression induction after exposure to other steroidal hormones (11-ketotestosterone ∼ testosterone > progesterone > cortisol > ethinylestradiol) correlated with their known binding affinities to zebrafish androgen receptor. Hence, these genes might represent potential markers for screening of androgenic compounds in the zebrafish embryo.</abstract><cop>United States</cop><pub>American Chemical Society</pub><pmid>26308493</pmid><doi>10.1021/acs.est.5b01034</doi><tpages>10</tpages></addata></record> |
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subjects | Androgen Antagonists - pharmacology Androgens Androgens - genetics Androgens - metabolism Animals Danio rerio Embryo, Nonmammalian - drug effects Embryos Environmental science Ethinyl Estradiol - pharmacology Female Freshwater Gene expression Gene Expression - drug effects Gene Expression Profiling Gene Expression Regulation, Developmental - drug effects Genes Hormones Humans Imidazolidines - pharmacology Receptors, Androgen - genetics Testosterone - analogs & derivatives Testosterone - pharmacology Zebrafish Zebrafish - embryology Zebrafish - genetics |
title | Identification and Characterization of Androgen-Responsive Genes in Zebrafish Embryos |
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