Modulation of collagen synthesis and mRNA by continuous and intermittent use of topical hydrocortisone in human skin

Abstract

Background: Glucocorticoids have been shown to downregulate collagen synthesis in human skin in vivo, thereby contributing to skin atrophy.

Objectives: To compare the effects of continuous and intermittent use of topical hydrocortisone on skin collagen synthesis and, furthermore, to elucidate the mechanism of collagen synthesis reduction induced by hydrocortisone.

Methods: Collagen propeptides reflecting the synthesis rate of type I and III collagens were studied from suction blister fluids in nine healthy subjects after 3 weeks of continuous (twice daily) or intermittent (on three consecutive days weekly) topical hydrocortisone treatment and 2 weeks after the termination of treatment. Type I collagen mRNA was studied in the same subjects from skin biopsies by using in situ hybridization (ISH) after 3 weeks of treatment.

Results: Three weeks of continuous treatment decreased the types I and III collagen propeptides in suction blister fluid by 89% and 82%, respectively, while intermittent treatment resulted in a corresponding decrease of 53% and 50%. ISH studies from skin biopsies showed type I collagen mRNA to be markedly reduced in fibroblasts after continuous and intermittent steroid treatment. After a 2-week drug-free interval, the synthesis rate was completely restored in both areas, and some subjects even showed upregulation of synthesis in previously steroid-treated skin.

Conclusions: Continuous hydrocortisone for 3 weeks markedly decreases collagen propeptides and corresponding mRNA in human skin. Intermittent hydrocortisone has a less marked effect on the collagen synthesis rate.