title: Glucocorticoid potentiation of cytochrome P4501A1 induction by 2,3,7,8-tetrachlorodibenzo-p-dioxin in porcine and human endothelial cells in culture.
abstract: Cytochrome P4501A1 (CYP1A1) induction was examined in cultures of porcine aorta endothelial cells (PAEC) and of human aorta endothelial cells (HAEC) exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) with or without the glucocorticoid receptor (GR) agonist cortisol or dexamethasone (DEX). In PAEC exposed to 0.1 nM TCDD + 10 microM cortisol the level of CYP1A1 protein and the degree of ethoxyresorufin-O-deethylase (EROD) activity induction were 2- to 3-fold greater than with 0.1 nM TCDD 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 microM DEX in the media. Cultures of HAEC also showed potentiation of EROD induction when 1 nM TCDD was co-administered with 10 microM DEX. This potentiation caused by DEX was abolished by addition of 10 microM of the GR antagonist RU38486. These data suggest that potentiation of CYP1A1 induction in endothelial cells proceeds by a GR dependent mechanism.
authors.affiliation: Biology Department, Woods Hole Oceanographic Institution, Massachusetts 02543, USA.
authors.forename: M
authors.initials: M
authors.lastname: Celander
authors.forename: R
authors.initials: R
authors.lastname: Weisbrod
authors.forename: J J
authors.initials: JJ
authors.lastname: Stegeman
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis*; D003907:Dexamethasone / Q000008:administration & dosage / Q000494:pharmacology*; D004357:Drug Synergism; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D006854:Hydrocortisone / Q000008:administration & dosage / Q000494:pharmacology*; D000072317:Polychlorinated Dibenzodioxins / Q000008:administration & dosage / Q000633:toxicity*; D011965:Receptors, Glucocorticoid / Q000819:agonists; D013552:Swine
chemical_list: D000072317:Polychlorinated Dibenzodioxins; D011965:Receptors, Glucocorticoid; D003907:Dexamethasone; D019363:Cytochrome P-450 CYP1A1; D006854:Hydrocortisone