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
Hauptverfasser: Fetter, Eva, Smetanová, Soňa, Baldauf, Lisa, Lidzba, Annegret, Altenburger, Rolf, Schüttler, Andreas, Scholz, Stefan
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container_end_page 11798
container_issue 19
container_start_page 11789
container_title Environmental science & technology
container_volume 49
creator Fetter, Eva
Smetanová, Soňa
Baldauf, Lisa
Lidzba, Annegret
Altenburger, Rolf
Schüttler, Andreas
Scholz, Stefan
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.
doi_str_mv 10.1021/acs.est.5b01034
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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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