GLUCOCORTICOID POTENTIATION OF CYTOCHROME P4501A1 INDUCTION BY 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN IN PORCINE AND HUMAN ENDOTHELIAL-CELLS IN CULTURE

Cytochrome P4501A1 (CYP1A1) induction was examined in cultures of porc ine aorta endothelial cells (PAEC) and of human aorta endothelial cell s (HAEC) exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) with or without the glucocorticoid receptor (GR) agonist cortisol or dexameth asone (DEX). In PAEC exposed to 0.1 nM TCDD + 10 mu M cortisol the lev el of CYP1A1 protein and the degree of ethoxyresorufin-O-deethylase (E ROD) activity induction were 2- to 3-fold greater than with 0.1 nM TCD D alone. A similar enhancement of EROD induction was obtained when 0.1 or 1 nM. TCDD was added together with 0.1, 1, or 10 mu M DEX in the m edia. Cultures of HAEC also showed potentiation of EROD induction when 1 nM TCDD was co-administered with 10 mu M DEX. This potentiation cau sed by DEX was abolished by addition of 10 mu M of the GR antagonist R U38486. These data suggest that potentiation of CYP1A1 induction in en dothelial cells proceeds by a GR dependent mechanism. (C) 1997 Academi c Press.