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The proposed mineralocorticoid-like signalling axis in teleost fish, consisting of the hormone 11-deoxycorticosterone (DOC) and a mineralocorticoid receptor (MR), has recently challenged our conception of cortisol being the only osmoregulatory corticosteroid in teleost fish. This paper aimed at comparing the osmoregulatory role of DOC with that of cortisol during the pre-adaptive development of SW-tolerance, smoltification, in Atlantic salmon. Using an in vitro gill block incubation system, the effect of DOC and cortisol in the gill was investigated from January to September, using Na(+),K(+)-ATPase α-subunit isoforms α-1a and α-1b mRNA levels as targets for regulation by the hormones. Cortisol and DOC both conferred significant up-regulation of α-1a and α-1b mRNA levels at specific time-points during smoltification. However, the effect of cortisol and DOC on α-subunit isoforms varied seasonally between isoforms and hormones. The maximum induction of α-1a was 3- to 4-fold compared to controls whereas a 2-fold induction was observed for α-1b. The pattern and capacity of stimulation of α-1a through smoltification were similar for cortisol and DOC, whereas cortisol had an enhanced capacity to stimulate α-1b as compared to DOC. Even though there was no demonstrable change in cortisol or DOC sensitivity in the gill, the magnitude of the hormonal effects were seasonally dependent. This is the first report of DOC-induced effects on osmoregulatory targets in fish, thus indicating a role for DOC and MR signalling in osmoregulation., (Copyright © 2010 Elsevier Inc. All rights reserved.)

The effect of corticosteroid hormones in fish are mediated through intracellular receptors that act as ligand-binding transcription factors. Many studies have been devoted to cortisol binding using radiolabeled ligand in fish and allowed characterization of a single class of high affinity binding sites in various tissues. Molecular characterization of cortisol receptors has only been initiated recently by cloning the different receptor forms: Following a isolation of a first glucocorticoid receptor (GR), a mineralocorticoid receptor (MR) was described and the presence of various GR isoforms was recently reported. Sequence comparison and phylogenetic analysis of these sequences confirm that fish possess both GR and MR and that GR gene is duplicated. The importance of these various corticosteroid receptor forms is also illustrated by analysis of their transcriptional activity. When tested in human cell lines, these receptors showed functionally distinct actions on GR-sensitive promotors, thus suggesting a more complicated corticosteroid signaling system than initially anticipated from binding studies. These results also suggest that, whereas cortisol is certainly the physiological ligand for GR, this may not be the case for MR which showed high sensitivity for deoxycorticosterone (DOC) and aldosterone. As this last hormone is probably absent in fish, these results raise the question as to whether DOC could be a physiological ligand for MR in fish. Information on DOC effect in fish is very scarce and clarification of the differential osmoregulatory roles of cortisol and DOC in fish needs ellucidation. This will require analysis of all actors of the corticosteroid signaling system at pre-receptor, receptor, and post-receptor levels.