title: RU486 inhibits induction of aromatase by dexamethasone via glucocorticoid receptor in cultured human skin fibroblasts.
abstract: Effects of RU486 on the induction of aromatase by dexamethasone via glucocorticoid receptor were determined using cultured human skin fibroblasts. Competition of [3H]dexamethasone binding to the cytosol receptor was 7 times stronger with RU486 than with dexamethasone. The order of the strength of competition was RU486 greater than dexamethasone greater than betamethasone greater than prednisolone greater than hydrocortisone. RU486 abolished a specific 8.6 S [3H]dexamethasone binding peak in the cytosol, determined using a sucrose density gradient analysis. Dexamethasone markedly induced aromatase and this event was strongly suppressed by RU486, in a dose-dependent manner, in the cultured skin fibroblasts. A linear correlation between the strength of competition and the induction of aromatase of various glucocorticoids was observed. RU486 non-competitively inhibited aromatase induction by dexamethasone determined from a double reciprocal plot of aromatase activity, with respect to [3H]androstenedione concentration in the presence of RU486. These results show that RU486 is a peripheral noncompetitive antiglucocorticoid on aromatase induction by glucocorticoid in human skin fibroblasts and that aromatase induction is a good marker for the biological function of glucocorticoid receptor in human skin fibroblasts.
authors.affiliation: Third Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Nawata
authors.forename: K
authors.initials: K
authors.lastname: Ono
authors.forename: M
authors.initials: M
authors.lastname: Ohashi
authors.forename: K
authors.initials: K
authors.lastname: Kato
authors.forename: H
authors.initials: H
authors.lastname: Ibayashi
mesh_terms: D047072:Aromatase Inhibitors; D002478:Cells, Cultured; D003907:Dexamethasone / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004963:Estrenes / Q000494:pharmacology*; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D006801:Humans; D015735:Mifepristone; D011965:Receptors, Glucocorticoid / Q000187:drug effects*; D012867:Skin / Q000166:cytology*; D013379:Substrate Specificity
chemical_list: D047072:Aromatase Inhibitors; D004963:Estrenes; D011965:Receptors, Glucocorticoid; C028697:dexamethasone receptor; D015735:Mifepristone; D003907:Dexamethasone