The effects of topical and systemic glucocorticosteroids on DNA synthesis in different tissues of the hairless mouse.
Two topical corticosteroids, clobetasol propionate and clobetasone butyrate, have been studied in hairless mice for their effects on DNA synthesis in the epidermis, thymus and spleen. Following topical application, both clobetasol propionate and clobetasone butyrate showed significant activity at the site of application throughout the range of concentrations tested (20 microliters; 0.0001-0.1%; 20 ng to 20 micrograms). However, whereas 20 ng clobetasol propionate also elicited significant effects in the distal (untreated) epidermis and the thymus, more than 2 micrograms of clobetasone butyrate were required to produce similar effects in these tissues. This finding was supported by the results obtained following intravenous administration of equivalent doses (0.01 and 0.001%; 200 microliters dose) of the same two steroids. Only clobetasol propionate showed significant activity in the epidermis and thymus. Clobetasone butyrate showed slight, non-significant effects in the epidermis at the highest concentration (200 microliters; 0.01%), but not in the thymus or spleen. An unexpected finding was that the effects following intravenous injection were generally lower than those following topical application. In conclusion, these results establish that (a) effects on DNA synthesis in the epidermis at a site distal to the application site are indicative of systemic activity from topically applied corticosteroids, (b) the thymus is especially sensitive to corticosteroids eliciting systemic effects and (c) an equivalent dose of a topical corticosteroid administered intravenously produces less inhibition of thymic and epidermal DNA synthesis than the same dose applied topically.
D000287:Administration, Topical; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001623:Betamethasone / Q000031:analogs & derivatives*; D002990:Clobetasol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004247:DNA / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D004817:Epidermis / Q000378:metabolism; D005260:Female; D007275:Injections, Intravenous; D008297:Male; D051379:Mice; D008812:Mice, Hairless; D013154:Spleen / Q000378:metabolism; D013950:Thymus Gland / Q000378:metabolism
D000893:Anti-Inflammatory Agents; C010893:clobetasone butyrate; D004247:DNA; D001623:Betamethasone; D002990:Clobetasol