Publication details

Identification and Characterization of Androgen-Responsive Genes in Zebrafish Embryos

Authors

FETTER Eva SMETANOVÁ Soňa BALDAUF Lisa LIDZBA Annegret ALTENBURGER Rolf SCHUTTLER Andreas SCHOLZ Stefan

Year of publication 2015
Type Article in Periodical
Magazine / Source Environmental Science and Technology
MU Faculty or unit

Faculty of Science

Citation
web http://pubs.acs.org/doi/10.1021/acs.est.5b01034
Doi http://dx.doi.org/10.1021/acs.est.5b01034
Field Environment influence on health
Keywords DISRUPTING CHEMICALS; DANIO-RERIO; FUNCTIONAL-CHARACTERIZATION; ENDOCRINE DISRUPTION; MODEL SELECTION; RAINBOW-TROUT; MESSENGER-RNA; THYROID-GLAND; EXPRESSION; RECEPTOR
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 similar to 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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