1 research outputs found
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 (EC<sub>50</sub> = 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 EC<sub>50</sub> 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