TRANSGENIC MOUSE MODEL PROVIDES A NOVEL BIOLOGICAL ASSAY OF TOPICAL GLUCOCORTICOSTEROID POTENCY

Background and Design: A homozygous line of transgenic mice that expre sses the human elastin promoter/CAT (chloramphenicol acetyltransferase ) reporter gene construct in a tissue-specific and developmentally reg ulated manner is presented. Previous studies have shown that subcutane ous injections of various glucocorticosteroids up-regulate the human t ransgene in the mouse skin potentially through their interaction with three putative glucocorticosteroid-responsive elements contained withi n the human elastin promoter. In this study, we propose the use of the se transgenic mice as a model system for assaying the potency of vario us topical glucocorticosteroid preparations. Results: In the first set of experiments, three different commercially available topical glucoc orticosteroid creams, 2.5% Hytone (2.5% hydrocortisone) (Dermik Labora tories, Fort Washington, Pa), Cutivate (0.05% fluticasone propionate) (Glare Inc, Research Triangle Park, NC), and Temovate (0.05% clobetaso l propionate) (Glare Inc) (being classified into class VII, V, and I s teroids, respectively) were applied to the skin of transgenic mice, wi th Eucerin (Beiersdorf Inc, Lindenhurst, NY) as the control cream. In a series of six experiments, Hytone 2.5% cream caused a 3.1-fold incre ase on the average, with Cutivate and Temovate creams resulting in 2.2 -fold and 12.4-fold increases in CAT activity over control, respective ly. Next, two different preparations of diflorasone diacetate 0.05% cr eam (Florone [class III] and Psorcon [class II], both from Dermik Labo ratories), formulated with different vehicles, were compared. Psorcon caused a 22.8-fold increase in CAT activity over the control compared with a 4.4-fold increase for Florone. However, an assay comparing Psor con ointment (class I) and Psorcon cream (class II) showed no statisti cally significant difference in their potencies. Conclusions: These pr eliminary findings suggest the usefulness of these transgenic mice as a model system for assaying the potency of topical glucocorticosteroid preparations. Discrepancies between our data and the published classi fication of some topical steroids may result from anatomic differences between human and murine skin, with mouse skin being much thinner. Al ternatively, the discrepancies may reflect the fact that our assay mea sures the biological activity of these steroids on gene transcription, while previous ranking is based on their vasoconstrictive activity.