Induction of cyclooxygenase-2 in thick ascending limb cells by adrenalectomy

Adrenalectomized (ADX) and sham-operated rats received either dexamethasone (DEX) or vehicle. Renal tissue was used fur morphologic analysis, assessme nt of cyclooxygenase-2 (COX-2) protein expression and mRNA accumulation, an d quantitation of COX-2 activity. In untreated or sham-operated rats, COX-2 protein was observed in a subset of tubular epithelial cells (<2%), which were located mainly in the cortex. All COX-2-positive cells also expressed Tamm-Horsfall glycoprotein, a highly selective marker for thick ascending l imb (TAL) cells. After ADX, >30% of TAL cells expressed COX-2 in a manlier consistent with recruitment of COX-2-positive TAL cells toward the medulla. Treatment of ADX rats with DEX reduced the number of COX-2-positive cells to that observed in sham-operated or intact rats. COX-2 mRNA accumulation w as increased by ADX and partially attenuated by treatment with DEX. Western blot analysis of cortical microsomes revealed a substantial increase in CO X-2 expression in ADX rats, compared with ADX/DEX-treated, sham-operated, o r intact rats. The increase in COX-2 protein expression was associated with a twofold increase in prostaglandin E-2 formation by cortical microsomes o btained from ADX rats, compared with sham-operated rats. It is concluded th at ADX induces expression of enzymatically active COX-2, such that expressi on occurs in the cortical TAL and proceeds in a defined pattern toward the outer medullary TAL. It is suggested that ADX induces expression of TAL cel ls that, in the basal state, do not express COX-2 protein.