title: Evolution of ligand specificity in vertebrate corticosteroid receptors.
abstract: BACKGROUND
  Corticosteroid receptors include mineralocorticoid (MR) and glucocorticoid (GR) receptors. Teleost fishes have a single MR and duplicate GRs that show variable sensitivities to mineralocorticoids and glucocorticoids. How these receptors compare functionally to tetrapod MR and GR, and the evolutionary significance of maintaining two GRs, remains unclear.
  
  
  RESULTS
  We used up to seven steroids (including aldosterone, cortisol and 11-deoxycorticosterone [DOC]) to compare the ligand specificity of the ligand binding domains of corticosteroid receptors between a mammal (Mus musculus) and the midshipman fish (Porichthys notatus), a teleost model for steroid regulation of neural and behavioral plasticity. Variation in mineralocorticoid sensitivity was considered in a broader phylogenetic context by examining the aldosterone sensitivity of MR and GRs from the distantly related daffodil cichlid (Neolamprologus pulcher), another teleost model for neurobehavioral plasticity. Both teleost species had a single MR and duplicate GRs. All MRs were sensitive to DOC, consistent with the hypothesis that DOC was the initial ligand of the ancestral MR. Variation in GR steroid-specificity corresponds to nine identified amino acid residue substitutions rather than phylogenetic relationships based on receptor sequences.
  
  
  CONCLUSIONS
  The mineralocorticoid sensitivity of duplicate GRs in teleosts is highly labile in the context of their evolutionary phylogeny, a property that likely led to neo-functionalization and maintenance of two GRs.
authors.affiliation: Department of Neurobiology and Behavior, Cornell University, Ithaca, NY 14853, USA.
authors.forename: Adam S
authors.initials: AS
authors.lastname: Arterbery
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Fergus
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Fogarty
authors.forename: John
authors.initials: J
authors.lastname: Mayberry
authors.forename: David L
authors.initials: DL
authors.lastname: Deitcher
authors.forename: W Lee
authors.initials: WL
authors.lastname: Kraus
authors.forename: Andrew H
authors.initials: AH
authors.lastname: Bass
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D024541:Batrachoidiformes / Q000235:genetics / Q000378:metabolism; D005075:Biological Evolution; D008024:Ligands; D051379:Mice; D008969:Molecular Sequence Data; D010802:Phylogeny; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011987:Receptors, Steroid / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D013045:Species Specificity; D013256:Steroids / Q000378:metabolism*; D014714:Vertebrates / Q000145:classification / Q000235:genetics / Q000378:metabolism*
chemical_list: D008024:Ligands; D011987:Receptors, Steroid; D013256:Steroids