PUBLICATION

Identification and characterisation of androgen-responsive genes in zebrafish embryos

Authors
Fetter, E., Smetanova, S., Baldauf, L., Lidzba, A., Altenburger, R., Schüttler, A., Scholz, S.
ID
ZDB-PUB-150827-2
Date
2015
Source
Environmental science & technology   49(19): 11789-98 (Journal)
Registered Authors
Keywords
none
Datasets
GEO:GSE59499
MeSH Terms
  • Androgen Antagonists/pharmacology
  • Androgens/genetics
  • Androgens/metabolism
  • Animals
  • Embryo, Nonmammalian/drug effects
  • Ethinyl Estradiol/pharmacology
  • Female
  • Gene Expression/drug effects
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental/drug effects*
  • Humans
  • Imidazolidines/pharmacology
  • Receptors, Androgen/genetics
  • Testosterone/analogs & derivatives*
  • Testosterone/pharmacology
  • Zebrafish/embryology*
  • Zebrafish/genetics
PubMed
26308493 Full text @ Env. Sci. Tech.
Abstract
Responsive genes for fish embryos have been identified so far for some endocrine pathways but not for androgens. Using transcriptome analysis and a multiple concentration-response modelling, we identified putative androgen-responsive genes in zebrafish embryos exposed to 0.05-5000 nM 11-ketotestosterone for 24 hours. Four selected genes with sigmoidal concentration-dependent expression profiles (EC50=6.5-30.0nM) were characterised 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 hypothesised 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.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping