title: 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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Department of Dermatology, University of Helsinki, Finland.
authors.forename: P
authors.initials: P
authors.lastname: Nuutinen
authors.forename: R
authors.initials: R
authors.lastname: Riekki
authors.forename: M
authors.initials: M
authors.lastname: Parikka
authors.forename: T
authors.initials: T
authors.lastname: Salo
authors.forename: P
authors.initials: P
authors.lastname: Autio
authors.forename: J
authors.initials: J
authors.lastname: Risteli
authors.forename: A
authors.initials: A
authors.lastname: Oikarinen
mesh_terms: D000287:Administration, Topical; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology*; D003094:Collagen / Q000096:biosynthesis* / Q000235:genetics; D004334:Drug Administration Schedule; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D006854:Hydrocortisone; D017403:In Situ Hybridization; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000096:biosynthesis / Q000235:genetics; D011347:Procollagen / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D012867:Skin / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D010446:Peptide Fragments; D011347:Procollagen; D012333:RNA, Messenger; C047202:procollagen Type I N-terminal peptide; C041876:procollagen Type III-N-terminal peptide; D003094:Collagen; D006854:Hydrocortisone