The effect of topical drugs on mouse ear epidermal transglutaminase activity.
The response of mouse ear epidermal transglutaminase to single applications of anthralin, retinoic acid (both 59 micrograms/ear) or fluocinolone acetonide (2 micrograms/ear) was determined. Anthralin and retinoic acid caused inflammation and accumulation of epidermal protein and DNA, whereas fluocinolone acetonide resulted in ear thinning and decreased epidermal protein and DNA. Treatment with either anthralin or retinoic acid caused increases in absolute amounts of epidermal transglutaminase activity/ear. Anthralin increased this parameter 70-100% above acetone-treated controls from 48 hr through 7 days. Retinoic acid-treated ears showed a slower initial increase but peaked at 4 times control level by 96 hr before returning to normal at 7 days. Fluocinolone acetonide treatment had no effect on this parameter. The specific activity of epidermal transglutaminase (total epidermal transglutaminase/total soluble epidermal protein) was decreased by retinoic acid treatment; was maintained at normal levels by anthralin (except for the 7-day point where it decreased 50%); and was dramatically stimulated by fluocinolone acetonide. In the latter case, specific activity was more than 5 x control by 96 hr and still near this level at 7 days. Epidermal transglutaminase activity is a marker of differentiation, and protein and DNA accumulation an indication of growth. Thus, at the doses studied, retinoic acid favors growth over differentiation, anthralin maintains a normal to near normal ratio of growth to differentiation, and fluocinolone acetonide strongly favors differentiation over growth.
D000287:Administration, Topical; D000818:Animals; D000873:Anthracenes / Q000008:administration & dosage*; D000875:Anthralin / Q000008:administration & dosage* / Q000494:pharmacology; D004796:Clinical Enzyme Tests; D004247:DNA / Q000032:analysis / Q000096:biosynthesis; D004423:Ear; D004817:Epidermis / Q000187:drug effects / Q000201:enzymology* / Q000502:physiology; D005260:Female; D005446:Fluocinolone Acetonide / Q000008:administration & dosage* / Q000494:pharmacology; D006128:Growth; D051379:Mice; D011506:Proteins / Q000032:analysis; D012885:Skinfold Thickness; D013997:Time Factors; D014212:Tretinoin / Q000008:administration & dosage* / Q000494:pharmacology; D005723:gamma-Glutamyltransferase / Q000096:biosynthesis / Q000378:metabolism*
D000873:Anthracenes; D011506:Proteins; D005446:Fluocinolone Acetonide; D014212:Tretinoin; D004247:DNA; D005723:gamma-Glutamyltransferase; D000875:Anthralin