Cortisol regulates Na(+) uptake in zebrafish, Danio rerio, larvae via the glucocorticoid receptor
- Authors
- Kumai, Y., Nesan, D., Vijayan, M.M., and Perry, S.F.
- ID
- ZDB-PUB-120927-13
- Date
- 2012
- Source
- Molecular and Cellular Endocrinology 364(1-2): 113-125 (Journal)
- Registered Authors
- Perry, Steve F.
- Keywords
- cortisol, glucocorticoid receptor, zebrafish, Rhcg1, Na+-H+ exchanger 3b, low ph
- MeSH Terms
-
- Acclimatization
- Aldosterone/pharmacology
- Ammonia/pharmacology
- Animals
- Anti-Inflammatory Agents/pharmacology*
- Cation Transport Proteins/antagonists & inhibitors
- Cation Transport Proteins/metabolism*
- Dexamethasone/pharmacology
- Hormone Antagonists/pharmacology
- Hydrocortisone/pharmacology*
- Hydrogen-Ion Concentration
- Ion Transport/drug effects
- Larva/drug effects
- Larva/physiology
- Mifepristone/pharmacology
- RNA, Small Interfering/genetics
- Receptors, Glucocorticoid/agonists
- Receptors, Glucocorticoid/antagonists & inhibitors
- Receptors, Glucocorticoid/metabolism*
- Receptors, Mineralocorticoid/agonists
- Receptors, Mineralocorticoid/metabolism
- Sodium/metabolism*
- Sodium-Hydrogen Exchangers/antagonists & inhibitors
- Sodium-Hydrogen Exchangers/metabolism*
- Zebrafish/physiology*
- Zebrafish Proteins/antagonists & inhibitors
- Zebrafish Proteins/metabolism*
- PubMed
- 22963886 Full text @ Mol. Cell. Endocrinol.
Unlike other freshwater fish previously examined, zebrafish are capable of increasing their rate of Na+ uptake during chronic exposure to acidic water (pH 4). In the present study, the potential role of cortisol in the induction of Na+ uptake during acid-exposure was investigated. When zebrafish larvae (4 days post-fertilization) were treated with waterborne cortisol, the rate of Na+ uptake was significantly increased; this effect was blocked by co-incubating larvae with RU-486, an antagonist selective for the glucocorticoid receptor (GR). A similar induction in Na+ uptake, which was also blocked by RU-486, was observed when larvae were treated with dexamethasone, a selective GR agonist. Conversely, treating larvae with aldosterone, a selective agonist for the mineralocorticoid receptor (MR) had no effect on Na+ uptake. Acid-exposure increased whole body cortisol levels and translational knockdown of GR using antisense morpholinos prevented the full induction of Na+ uptake during exposure to acidic water, further confirming the role of cortisol and GR in Na+ uptake stimulation. Using immunohistochemistry, GR was localized to ionocytes known to be responsible for Na+ uptake (HR-cells). Knockdown of Rhcg1, an apical membrane ammonia channel or Na+/H+ exchanger 3b (NHE3b), proteins known to play an important role in facilitating Na+ uptake in acidic water, prevented the stimulatory effects of cortisol treatment on Na+ uptake, suggesting that cortisol regulates Na+ uptake by stimulating an Rhcg1–NHE3b “functional metabolon”.