Cortisol regulates Na+ uptake in zebrafish, Danio rerio, larvae via the glucocorticoid receptor.

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".