RU486 inhibits induction of aromatase by dexamethasone via glucocorticoid receptor in cultured human skin fibroblasts.
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.
Nawata
H
H
Third Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Ono
K
K
Ohashi
M
M
Kato
K
K
Ibayashi
H
H
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
D047072:Aromatase Inhibitors; D004963:Estrenes; D011965:Receptors, Glucocorticoid; C028697:dexamethasone receptor; D015735:Mifepristone; D003907:Dexamethasone