A transgenic mouse model provides a novel biological assay of topical glucocorticosteroid potency.
METHODS
A homozygous line of transgenic mice that expresses the human elastin promoter/CAT (chloramphenicol acetyltransferase) reporter gene construct in a tissue-specific and developmentally regulated manner is presented. Previous studies have shown that subcutaneous injections of various glucocorticosteroids up-regulate the human transgene in the mouse skin potentially through their interaction with three putative glucocorticosteroid-responsive elements contained within the human elastin promoter. In this study, we propose the use of these transgenic mice as a model system for assaying the potency of various topical glucocorticosteroid preparations.


RESULTS
In the first set of experiments, three different commercially available topical glucocorticosteroid creams, 2.5% Hytone (2.5% hydrocortisone) (Dermik Laboratories, Fort Washington, Pa), Cutivate (0.05% fluticasone propionate) (Glaxo Inc, Research Triangle Park, NC), and Temovate (0.05% clobetasol propionate) (Glaxo Inc) (being classified into class VII, V, and I steroids, respectively) were applied to the skin of transgenic mice, with Eucerin (Beiersdorf Inc, Lindenhurst, NY) as the control cream. In a series of six experiments, Hytone 2.5% cream caused a 3.1-fold increase on the average, with Cutivate and Temovate creams resulting in 2.2-fold and 12.4-fold increases in CAT activity over control, respectively. Next, two different preparations of diflorasone diacetate 0.05% cream (Florone [class III] and Psorcon [class II], both from Dermik Laboratories), 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 Psorcon ointment (class I) and Psorcon cream (class II) showed no statistically significant difference in their potencies.


CONCLUSIONS
These preliminary 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 classification of some topical steroids may result from anatomic differences between human and murine skin, with mouse skin much thinner, Alternatively, the discrepancies may reflect the fact that our assay measures the biological activity of these steroids on gene transcription, while previous ranking is based on their vasoconstrictive activity.
Katchman
S D
SD
Department of Dermatology, Jefferson Medical College, Philadelphia, PA, USA.
Del Monaco
M
M
Wu
M
M
Brown
D
D
Hsu-Wong
S
S
Uitto
J
J
D000287:Administration, Topical; D000730:Androstadienes / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001681:Biological Assay; D002990:Clobetasol / Q000031:analogs & derivatives* / Q000494:pharmacology; D000068298:Fluticasone; D005938:Glucocorticoids; D006854:Hydrocortisone; D051379:Mice; D008822:Mice, Transgenic
D000730:Androstadienes; D000893:Anti-Inflammatory Agents; D005938:Glucocorticoids; D002990:Clobetasol; D000068298:Fluticasone; D006854:Hydrocortisone