Development of the corticosteroid stress axis and receptor expression in zebrafish.

Using zebrafish embryos and larvae, we examined the temporal patterns of cortisol and expression of genes involved in corticosteroid synthesis and signaling. Embryonic cortisol levels decreased approximately 70% from 1.5 h postfertilization (hpf) to hatch (approximately 42 hpf) and then increased 27-fold by 146 hpf. The mRNA abundances of steroidogenic acute regulatory protein, 11beta-hydroxylase and 11beta-hydroxysteroid dehydrogenase type 2, increased severalfold after hatch and preceded the rise of cortisol levels. In contrast to other teleosts that possess two glucocorticoid receptors (GRs) and one mineralocorticoid receptor (MR), only one GR and MR were identified in zebrafish, which were cloned and sequenced. GR mRNA abundance decreased from 1.5 to 25 hpf, rebounded, and then was stable from 49 to 146 hpf. MR transcripts increased continuously from 1.5 hpf and were 52-fold higher by 97 hpf. An acute cortisol response to a stressor was not detected until 97 hpf, whereas melanocortin type 2 receptor mRNA increased between 25 and 49 hpf. Collectively, the patterns of cortisol and the expression of cortisol biosynthetic genes and melanocortin type 2 receptor suggest that the corticoid stress axis in zebrafish is fully developed only after hatch. The temporal differences in GR, MR, and 11beta-hydroxysteroid dehydrogenase type 2 gene expression lead us to propose a key role for MR signaling by maternal cortisol during embryogenesis, whereas cortisol secretion after hatch may be regulating GR expression and signaling in zebrafish.