title: Role of glucocorticoid receptor in acclimation of killifish (Fundulus heteroclitus) to seawater and effects of arsenic.
abstract: Killifish are euryhaline teleosts that adapt to rapid changes in the salinity of the seawater. It is generally accepted that acclimation to seawater is mediated by cortisol activation of the glucocorticoid receptor (GR), which stimulates CFTR mRNA expression and CFTR-mediated Cl- secretion by the gill. Because there is no direct evidence in killifish that the GR stimulates CFTR gene expression, quantitative PCR studies were conducted to test the hypothesis that cortisol activation of GR upregulates CFTR mRNA expression and that this response is required for acclimation to seawater. Inhibition of the GR by RU-486 prevented killifish from acclimating to increased salinity and blocked the increase in CFTR mRNA. In contrast, inhibition of the mineralocorticoid receptor by spironolactone had no effect on acclimation to seawater. Thus acclimation to increased salinity in killifish requires signaling via the GR and includes an increase in CFTR gene expression. Because arsenic, a toxic metalloid that naturally occurs in the aquatic environment, has been shown to disrupt GR transcriptional regulation in avian and mammalian systems, studies were also conducted to determine whether arsenic disrupts cortisol-mediated activation of CFTR gene expression in this in vivo fish model and thereby blocks the ability of killifish to acclimate to increased salinity. Arsenic prevented acclimation to seawater and decreased CFTR protein abundance. However, arsenic did not disrupt the GR-induced increase in CFTR mRNA. Thus arsenic blocks acclimation to seawater in killifish by a mechanism that does not disrupt GR-mediated induction of CFTR gene expression.
authors.affiliation: Department of Physiology, Dartmouth College, Dartmouth Medical School, N. College St., Hanover, NH 03755, USA.
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Shaw
authors.forename: Kristen
authors.initials: K
authors.lastname: Gabor
authors.forename: Emily
authors.initials: E
authors.lastname: Hand
authors.forename: Alexander
authors.initials: A
authors.lastname: Lankowski
authors.forename: Lydia
authors.initials: L
authors.lastname: Durant
authors.forename: Renee
authors.initials: R
authors.lastname: Thibodeau
authors.forename: Caitlin R
authors.initials: CR
authors.lastname: Stanton
authors.forename: Roxanna
authors.initials: R
authors.lastname: Barnaby
authors.forename: Bonita
authors.initials: B
authors.lastname: Coutermarsh
authors.forename: Katherine H
authors.initials: KH
authors.lastname: Karlson
authors.forename: J Denry
authors.initials: JD
authors.lastname: Sato
authors.forename: Joshua W
authors.initials: JW
authors.lastname: Hamilton
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Stanton
mesh_terms: D000064:Acclimatization / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D001151:Arsenic / Q000493:pharmacokinetics / Q000633:toxicity*; D015153:Blotting, Western; D002712:Chlorides / Q000378:metabolism; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000096:biosynthesis / Q000235:genetics; D023781:Fundulidae / Q000502:physiology*; D005880:Gills / Q000378:metabolism; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology; D006727:Hormone Antagonists / Q000494:pharmacology; D006854:Hydrocortisone / Q000494:pharmacology; D013058:Mass Spectrometry; D015735:Mifepristone / Q000494:pharmacology; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors / Q000502:physiology*; D018161:Receptors, Mineralocorticoid / Q000187:drug effects / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012623:Seawater; D028021:Sodium-Potassium-Chloride Symporters / Q000096:biosynthesis / Q000235:genetics; D000254:Sodium-Potassium-Exchanging ATPase / Q000096:biosynthesis / Q000235:genetics; D064506:Solute Carrier Family 12, Member 2; D013148:Spironolactone / Q000494:pharmacology; D014018:Tissue Distribution
chemical_list: D002712:Chlorides; D006727:Hormone Antagonists; D000451:Mineralocorticoid Receptor Antagonists; D011965:Receptors, Glucocorticoid; D018161:Receptors, Mineralocorticoid; D028021:Sodium-Potassium-Chloride Symporters; D064506:Solute Carrier Family 12, Member 2; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D013148:Spironolactone; D015735:Mifepristone; D000254:Sodium-Potassium-Exchanging ATPase; D001151:Arsenic; D006854:Hydrocortisone