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-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 <i>cyp2k22</i> and <i>slco1f4</i> was demonstrated in the pronephros; <i>lipca</i> was detected in the liver, and <i>sult2st3</i> 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 <i>sult2st3</i> and <i>cyp2k22</i> 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 <i>sult2st3</i> and <i>cyp2k22</i> 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