11-BETA-HYDROXYSTEROID DEHYDROGENASE, MINERALOCORTICOID RECEPTOR, ANDTHIAZIDE-SENSITIVE NA-CL COTRANSPORTER EXPRESSION BY DISTAL TUBULES

Mineralocorticoid hormones regulate salt transport along the distal ne phron by binding to intracellular receptors and activating gene transc ription. Previous experiments showed that systemic aldosterone infusio ns stimulate thiazide-sensitive Na and Cl transport by distal convolut ed tubule (DCT) cells; this effect could have been direct or secondary to systemic hormonal effects. Aldosterone target tissues express both mineralocorticoid receptors and the metabolic enzyme 11 beta-hydroxys teroid dehydrogenase type 2, Mineralocorticoid receptors have been loc alized to the DCT in some experiments, but not in others. Expression o f 11 beta-hydroxysteroid dehydrogenase type 2 by DCT cells has not bee n investigated. The present experiments were designed to test the hypo thesis that rat DCT cells are targets of aldosterone action. Patterns of mineralocorticoid receptor, 11 beta-hydroxysteroid dehydrogenase, t hiazide-sensitive Na-CI cotransporter, and Na/Ca exchanger expression along the distal tubule were examined. A polyclonal antibody was gener ated to localize the thiazide-sensitive Na-Cl cotransporter. Thiazide- sensitive Na-Cl cotransporter and 11 beta-hydroxysteroid dehydrogenase expression were examined using both in situ hybridization and immunoc ytochemistry; Na/Ca exchanger and mineralocorticoid receptor expressio n were examined by immunocytochemistry. The results indicate that 11 b eta-hydroxysteroid dehydrogenase is expressed by DCT cells, as well as connecting tubule cells and principal cells of the collecting duct; e xpression levels are low near the junction with the thick ascending li mb and rise near the transition to the connecting tubule. Mineralocort icoid receptors are expressed by DCT cells, as well as along the thick ascending limb, connecting tubule, and collecting duct. The results i ndicate that components of the mineralocorticoid receptor system are e xpressed by DCT cells, suggesting that these cells are targets of aldo sterone action.