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

Br J Dermatol. 2003 Jan;148(1):39-45. doi: 10.1046/j.1365-2133.2003.05018.x.


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.

MeSH terms

  • Administration, Topical
  • Adult
  • Anti-Inflammatory Agents / administration & dosage
  • Anti-Inflammatory Agents / pharmacology*
  • Collagen / biosynthesis*
  • Collagen / genetics
  • Drug Administration Schedule
  • Female
  • Gene Expression Regulation / drug effects
  • Humans
  • Hydrocortisone
  • In Situ Hybridization
  • Male
  • Middle Aged
  • Peptide Fragments / biosynthesis
  • Peptide Fragments / genetics
  • Procollagen / biosynthesis
  • Procollagen / genetics
  • RNA, Messenger / genetics
  • Skin / drug effects*
  • Skin / metabolism


  • Anti-Inflammatory Agents
  • Peptide Fragments
  • Procollagen
  • RNA, Messenger
  • procollagen Type I N-terminal peptide
  • procollagen Type III-N-terminal peptide
  • Collagen
  • Hydrocortisone