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Glucocorticoids modulate renal glucocorticoid receptors and Na-K ATPase activity
D Ellis1, T D Sothi, E D Avner
1Children's Hospital of Pittsburgh, Department of Pediatrics, University of Pittsburgh School of Medicine, Pennsylvania.
Abstract:
Primary cultures of mouse renal tubular epithelial cells were used to study the effect of hydrocortisone on the regulation of glucocorticoid receptors (GR) and on sodium-potassium adenosine triphosphatase (Na-K ATPase) activity. A GR assay was developed and performed directly on cell monolayers maintained in serum-free medium to which hydrocortisone at 5 nM, 50 nM, and 5 X 10(-4) M was added. Compared with control cells grown in medium without hydrocortisone, GR levels per cell decreased by 50% after 48 hours of growth in medium containing 5 nM hydrocortisone concentrations (50 nM or 5 X 10(-4) M), GR levels decreased to less than or equal to 28% of control values. In all hydrocortisone treatment groups there was an inverse relation between GR concentrations and Na-K ATPase activity. Binding of cell GR by the addition of the antiglucocorticoid RU 38486 in hydrocortisone-supplemented medium eliminated the glucocorticoid-induced stimulation of Na-K ATPase activity. These results demonstrate a time- and dose-dependent effect of glucocorticoids on GR binding activity and a direct relation between this receptor-hormone interaction and Na-K ATPase activity in intact renal tubular epithelial cells.
Insights
Hydrocortisone treatment in mouse kidney cells reduces glucocorticoid receptors (GR) and increases Na-K ATPase activity. This suggests a direct link between GR regulation and renal sodium-potassium pump function.
Area of Science:
- Nephrology
- Endocrinology
- Cell Biology
Background:
- Glucocorticoids play a crucial role in regulating various physiological processes.
- Glucocorticoid receptors (GR) mediate the effects of glucocorticoids.
- Sodium-potassium adenosine triphosphatase (Na-K ATPase) is vital for maintaining cell function, particularly in the kidneys.
Purpose of the Study:
- To investigate the impact of hydrocortisone on glucocorticoid receptor (GR) regulation.
- To examine the effect of hydrocortisone on Na-K ATPase activity in renal tubular epithelial cells.
- To determine the relationship between GRs and Na-K ATPase activity.
Main Methods:
- Primary cultures of mouse renal tubular epithelial cells were utilized.
- A GR assay was developed and performed on cell monolayers.
- Cells were treated with varying concentrations of hydrocortisone (5 nM, 50 nM, 5 X 10(-4) M) or an antiglucocorticoid (RU 38486).
- Na-K ATPase activity was measured.
Main Results:
- Hydrocortisone treatment led to a dose- and time-dependent decrease in GR levels per cell.
- GR levels decreased by up to 50% with 5 nM hydrocortisone and over 72% with higher concentrations.
- An inverse relationship was observed between GR concentrations and Na-K ATPase activity.
- Blocking GR with RU 38486 abolished the hydrocortisone-induced stimulation of Na-K ATPase activity.
Conclusions:
- Glucocorticoids exert a time- and dose-dependent effect on GR binding activity in renal tubular cells.
- There is a direct relationship between the GR-hormone interaction and Na-K ATPase activity.
- These findings highlight the role of glucocorticoids in modulating renal tubular cell function.