Evolution of the corticosteroid receptor signalling pathway in fish.

The corticosteroid receptors (CR) control a vast array of physiological processes acting primarily as ligand-dependent transcription factors. The origins of the gnathostomata CRs can be traced back to an ancestral steroid receptor present in a primitive agnathan vertebrate. A genome duplication event in the early gnathostomes is believed to have produced a set of two CRs still present today in Sarcopterygii (lobe-finned fish and tetrapods), i.e. a glucocorticoid (GR) and mineralocorticoid receptor (MR), with divergent function and different ligands, cortisol and aldosterone, respectively. A further genome duplication occurred in the early evolutionary history of the teleosts, and the teleost CR system seems to have diversified, consisting now of 2 GRs and a MR. Teleosts lack aldosterone and the main corticosteroid is believed to be cortisol. However, the mineralocorticoid, 11-deoxycorticosterone (DOC), has been identified as an agonist for the rainbow trout MR, suggesting it may be the ancestral ligand for the MR. The retention of two GRs in teleosts suggests neofunctionalisation of one of the duplicated genes, but this hypothesis requires further work. In rainbow trout, transactivation and transrepression activities of the two GRs show marked differences in their sensitivity to glucocorticoids, suggesting a mechanism that may allow the two GRs to control different physiological pathways. Whether a similar mechanism is seen throughout the actinopterygii or whether this is specific to the salmonid lineage remains to be verified.