The molecular basis of glucocorticoid-induced skin atrophy: topical glucocorticoid apparently decreases both collagen synthesis and the correspondingcollagen mRNA level in human skin in vivo

The effects of topical betamethasone-17-valerate on collagen propeptide lev els, collagen mRNA level, lysyl oxidase mRNA and matrix metalloproteinase ( MMP)-1 and MMP-2 mRNA levels were studied in human skin. Three days' treatm ent of healthy skin with topical betamethasone caused a 70-80% decrease in type I and III collagen propeptides in suction blister fluid, A similar dec rease was found in type I collagen mRNA when assayed by either slot-blot hy bridization or a quantitative polymerase chain reaction method, indicating that the decrease in collagen synthesis after topical glucocorticoid treatm ent is apparently due to a decrease in corresponding mRNA, mRNA of lysyl ox idase, which is an important enzyme catalysing the cross-linking of collage n chains, and collagen-degrading enzyme MMP-1 and MMP-2 mRNAs were not decr eased in the same skin samples. This suggests that in vivo glucocorticoids modulate variably the genes involved in collagen synthesis and degradation. Our study provides a solid molecular basis for glucocorticoid-induced derm al atrophy, which results from the decrease in functional collagen mRNA in the skin.