title: Corticosteroid receptors involved in stress regulation in common carp, Cyprinus carpio.
abstract: In higher vertebrates, mineralo- (aldosterone) and glucocorticoids (cortisol/corticosterone) exert their multiple actions via specific transcription factors, glucocorticoid (GR) and mineralocorticoid (MR) receptors. Teleostean fishes lack aldosterone and mineral regulatory processes seem under dominant control by cortisol. Despite the absence of the classical mineralocorticoid aldosterone, teleostean fishes do have an MR with cortisol and possibly 11-deoxycorticosterone (DOC) (as alternative for aldosterone) as predominant ligands. We studied corticoid receptors in common carp (Cyprinus carpio L). Through homology cloning and bioinformatic analysis, we found duplicated GR genes and a single MR gene. The GR genes likely result from a major genomic duplication event in the teleostean lineage; we propose that the gene for a second MR was lost. Transactivation studies show that the carp GRs and MR have comparable affinity for cortisol; the MR has significantly higher sensitivity to DOC, and this favours a role for DOC as MR ligand in fish physiology. mRNA of the GRs and the MR is expressed in forebrain (in pallial areas homologous to mammalian hippocampus), corticotrophin-releasing hormone (CRH) cells in the pre-optic nucleus (NPO) and pituitary pars distalis ACTH cells, three key neural/endocrine components of the stress axis. After exposure to prolonged and strong (not to mild acute) stressors, mRNA levels of both GRs and MR become down-regulated in the brain, but not in the NPO CRH cells or pituitary ACTH cells. Our data predicts a function in stress physiology for all CRs and suggest telencephalon as a first line cortisol target in stress.
authors.affiliation: Department of Animal Physiology, Radboud University, Toernooiveld 1, 6525 ED Nijmegen, The Netherlands.
authors.forename: Ellen H
authors.initials: EH
authors.lastname: Stolte
authors.forename: Aurélia F
authors.initials: AF
authors.lastname: de Mazon
authors.forename: Karen M
authors.initials: KM
authors.lastname: Leon-Koosterziel
authors.forename: Maria
authors.initials: M
authors.lastname: Jesiak
authors.forename: Nic R
authors.initials: NR
authors.lastname: Bury
authors.forename: Armin
authors.initials: A
authors.lastname: Sturm
authors.forename: Huub F J
authors.initials: HF
authors.lastname: Savelkoul
authors.forename: B M Lidy Verburg
authors.initials: BM
authors.lastname: van Kemenade
authors.forename: Gert
authors.initials: G
authors.lastname: Flik
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002347:Carps / Q000235:genetics / Q000502:physiology*; D019295:Computational Biology; D029941:Fish Proteins / Q000235:genetics / Q000502:physiology; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008969:Molecular Sequence Data; D010802:Phylogeny; D016548:Prosencephalon / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D011965:Receptors, Glucocorticoid / Q000145:classification / Q000235:genetics / Q000502:physiology; D018161:Receptors, Mineralocorticoid / Q000145:classification / Q000235:genetics / Q000502:physiology; D011987:Receptors, Steroid / Q000145:classification / Q000235:genetics / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D013312:Stress, Physiological / Q000502:physiology*
chemical_list: D029941:Fish Proteins; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D018161:Receptors, Mineralocorticoid; D011987:Receptors, Steroid