title: Identification and Characterization of Androgen-Responsive Genes in Zebrafish Embryos.
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.
authors: UFZ - Helmholtz Centre for Environmental Research , Department Bioanalytical Ecotoxicology, Permoserstraße 15, 04318 Leipzig, Germany.
authors: Eva
authors: E
authors: Fetter
authors: UFZ - Helmholtz Centre for Environmental Research , Department Bioanalytical Ecotoxicology, Permoserstraße 15, 04318 Leipzig, Germany.|RECETOX - Research Centre for Toxic Compounds in the Environment, Masaryk University , Faculty of Science, Kamenice 753/5, 625 00 Brno, Czech Republic.
authors: Soňa
authors: S
authors: Smetanová
authors: UFZ - Helmholtz Centre for Environmental Research , Department Bioanalytical Ecotoxicology, Permoserstraße 15, 04318 Leipzig, Germany.
authors: Lisa
authors: L
authors: Baldauf
authors: UFZ - Helmholtz Centre for Environmental Research , Department Bioanalytical Ecotoxicology, Permoserstraße 15, 04318 Leipzig, Germany.
authors: Annegret
authors: A
authors: Lidzba
authors: UFZ - Helmholtz Centre for Environmental Research , Department Bioanalytical Ecotoxicology, Permoserstraße 15, 04318 Leipzig, Germany.
authors: Rolf
authors: R
authors: Altenburger
authors: UFZ - Helmholtz Centre for Environmental Research , Department Bioanalytical Ecotoxicology, Permoserstraße 15, 04318 Leipzig, Germany.
authors: Andreas
authors: A
authors: Schüttler
authors: UFZ - Helmholtz Centre for Environmental Research , Department Bioanalytical Ecotoxicology, Permoserstraße 15, 04318 Leipzig, Germany.
authors: Stefan
authors: S
authors: Scholz
mesh_terms: D000726:Androgen Antagonists / Q000494:pharmacology; D000728:Androgens / Q000235:genetics / Q000378:metabolism; D000818:Animals; D004625:Embryo, Nonmammalian / Q000187:drug effects; D004997:Ethinyl Estradiol / Q000494:pharmacology; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D006801:Humans; D048289:Imidazolidines / Q000494:pharmacology; D011944:Receptors, Androgen / Q000235:genetics; D013739:Testosterone / Q000031:analogs & derivatives* / Q000494:pharmacology; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics
chemical_list: D000726:Androgen Antagonists; D000728:Androgens; D048289:Imidazolidines; D011944:Receptors, Androgen; D013739:Testosterone; D004997:Ethinyl Estradiol; C021277:nilutamide; C003600:11-ketotestosterone