Regulation of glucocorticoid receptors and Na-K ATPase activity by hydrocortisone in proximal tubular epithelial cells.
The effect of hydrocortisone (HC) in modulating glucocorticoid receptors (GR) and sodium-potassium adenosine triphosphatase (Na-K ATPase) activity was studied in primary cultures of immunoisolated murine proximal tubular epithelial cells (PTEC). Utilizing monoclonal antibody against stage-specific embryonic antigen-1, a homogeneous population of PTEC was obtained in high yield. The cells were cultured to confluence and further treated for 48 h in serum-free growth medium containing no HC (control); 50 nM HC; or 50 nM HC plus 20 nM of the antiglucocorticoid, RU 38486. PTEC treated with 50 nM HC had 56% of GR binding and 160% Na-K ATPase activity as compared to controls (P less than 0.01). GR binding was abolished by incubation in RU 38486 whereas Na-K ATPase fell below control values (P less than 0.05). Brief incubations of HC-treated PTEC with 0.5 mM ouabain resulted in a fall in GR binding without a change in Na-K ATPase activity. These data indicate that in PTEC, HC regulates GR binding and they suggest that stimulation of Na-K ATPase activity is a direct biological response to this receptor-hormone interaction. Thus, primary cultures of immunoaffinity-isolated PTEC offer a good model system for investigating the molecular basis underlying the regulation of GR binding and postreceptor events influenced by glucocorticoids.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D002469:Cell Separation; D002478:Cells, Cultured; D004963:Estrenes / Q000494:pharmacology; D006593:Hexokinase / Q000378:metabolism; D006854:Hydrocortisone / Q000494:pharmacology*; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D015735:Mifepristone; D010042:Ouabain / Q000494:pharmacology; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D013997:Time Factors; D005723:gamma-Glutamyltransferase / Q000378:metabolism
D000911:Antibodies, Monoclonal; D004963:Estrenes; D011965:Receptors, Glucocorticoid; D015735:Mifepristone; D010042:Ouabain; D005723:gamma-Glutamyltransferase; D006593:Hexokinase; D000254:Sodium-Potassium-Exchanging ATPase; D006854:Hydrocortisone