Effect of RU 486 on the atrophogenic and antiinflammatory effects of glucocorticoids in skin.
Clobetasol-17-propionate (CP), a synthetic glucocorticoid (GC), reduced skin thickness in rats. Both the subcutaneous injection and topical applications of RU 486 counteracted CP-induced reduction in skin thickness. Topical application of the CP cream completely inhibited the ear edema produced by croton oil. A less potent GC, hydrocortisone-17-butyrate, also inhibited ear edema. This antiinflammatory effect was not abolished by the subcutaneous injection or topical application of RU 486. These observations suggest that GC-induced skin atrophy is mediated by glucocorticoid receptors (GRs), while the inhibition of croton oil-induced inflammation by GC is primarily related to the direct effects of GC, which are not mediated by GRs. Our findings suggest that RU 486 inhibits the atrophogenic effect of GCs without interfering with their antiinflammatory effect. Dissociation of antiinflammatory and atrophogenic activity of GC seems favorable in treating inflammatory skin diseases lacking epidermal proliferation.
Department of Dermatology, Faculty of Medicine, Tottori University, Yonago, Japan.
K
K
Iwasaki
E
E
Mishima
M
M
Miura
N
N
Sakai
S
S
Shimao
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001284:Atrophy; D002990:Clobetasol / Q000031:analogs & derivatives / Q000494:pharmacology; D003436:Croton Oil; D003907:Dexamethasone / Q000378:metabolism; D004427:Ear Diseases / Q000139:chemically induced / Q000188:drug therapy; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D005938:Glucocorticoids / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D008024:Ligands; D008297:Male; D015735:Mifepristone / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D012867:Skin / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*
D000893:Anti-Inflammatory Agents; D005938:Glucocorticoids; D008024:Ligands; D011965:Receptors, Glucocorticoid; D015735:Mifepristone; D003907:Dexamethasone; D003436:Croton Oil; D002990:Clobetasol