Aldosterone decreases UT-A1 urea transporter expression via the mineralocorticoid receptor

Adrenalectomy in rats is associated with urinary concentrating and diluting defects. This study tested the effect of adrenal steroids on the UT-A l urea transporter because it is involved in the urine-concentrating mechanism. Rats were adrenalectomized and given normal saline for 14 d, after which they received (1) vehicle, (2) aldosterone, or (3) spironolactone plus aldosterone. Adrenalectomy alone significantly increased UT-A l protein in the inner medullary tip after 7 d, whereas aldosterone repletion reversed the effect. Spironolactone blocked the aldosterone-induced decrease in UT-A l, indicating that aldosterone was workin-via the mineralocorticoid receptor. For verifying that glucocorticoids downregulate UT-A l protein through a different receptor, three groups of adrenalectomized rats were prepared: (1) vehicle, (2) adrenalectomy plus dexamethasone, and (3) adrenalectomy plus dexamethasone and spironolactone. Dexamethasone significantly reversed UT-A l protein abundance increase in the inner medullary tip of adrenalectomized rats. When spironolactone was given with dexamethasone, it did not affect the dexamethasone-induced decrease in UT-A l There was no significant change in serum vasopressin level, aquaporin 2, or Na+-K+-2Cl(-) co-transporter NKCC2/BSC1 protein abundances or UT-A l mRNA abundance in any of the groups. In conclusion, either mineralocorticoids or alucocorticoids can downregulate UT-A l protein. The decrease in UT-A l does not require both steroid hormones, and each works through a different receptor.