title: Induction of collagen by estradiol: difference between sun-protected and photodamaged human skin in vivo.
abstract: OBJECTIVE
  To evaluate the effectiveness of topical estradiol in stimulating collagen I and III production in naturally aged and photoaged human skin of postmenopausal women and age-matched men.
  
  
  METHODS
  Vehicle-controlled treatment followed by biochemical and immunohistochemical analyses of skin biopsy specimens.
  
  
  METHODS
  Academic referral center.
  
  
  METHODS
  Seventy healthy volunteers (40 postmenopausal women with a mean age of 75 years, and 30 men with a mean age of 75 years) with photodamaged skin. Interventions Topical application of estradiol, 0.01%, 0.1%, 1%, or 2.5% or vehicle on aged or photoaged skin, with biopsy specimens taken after last treatment.
  
  
  METHODS
  De novo synthesis of collagen by quantitative polymerase chain reaction, immunohistochemistry, and enzyme-linked immunosorbent assay.
  
  
  RESULTS
  Topical estradiol increased procollagen I and III messenger RNA and collagen I protein levels in sun-protected aged hip skin in postmenopausal women and, to a lesser extent, in age-matched men. Surprisingly, no significant changes in production were observed in women or men after 2-week estradiol treatment of photoaged forearm or face skin, despite similar expression of estrogen receptors (ER-alpha, ER-beta, and GPR30) in aged and photoaged skin. Estradiol treatment induced the estrogen-responsive gene GREB1, indicating that penetration of topical estradiol and genomic response to estrogen were similar in the 3 anatomic sites.
  
  
  CONCLUSIONS
  Two-week topical estradiol treatment stimulates collagen production in sun-protected hip skin, but not in photoaged forearm or face skin, in postmenopausal women and aged-matched men. These findings suggest that menopause-associated estrogen decline is involved in reduced collagen production in sun-protected skin. Interestingly, alterations induced by long-term sun exposure hinder the ability of topical 2-week estradiol to stimulate collagen production in aged skin.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT00113100.
authors.affiliation: Department of Dermatology, University of Michigan Medical School, Ann Arbor, MI 48109-0609, USA.
authors.forename: Laure
authors.initials: L
authors.lastname: Rittié
authors.forename: Sewon
authors.initials: S
authors.lastname: Kang
authors.forename: John J
authors.initials: JJ
authors.lastname: Voorhees
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Fisher
mesh_terms: D000287:Administration, Topical; D000368:Aged; D000369:Aged, 80 and over; D024042:Collagen Type I / Q000096:biosynthesis*; D024061:Collagen Type III / Q000096:biosynthesis*; D004334:Drug Administration Schedule; D004781:Environmental Exposure; D004958:Estradiol / Q000008:administration & dosage* / Q000494:pharmacology; D005145:Face; D005260:Female; D005542:Forearm; D005786:Gene Expression Regulation / Q000187:drug effects; D006615:Hip; D006801:Humans; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics; D017698:Postmenopause; D011347:Procollagen / Q000096:biosynthesis; D011835:Radiation Protection; D011960:Receptors, Estrogen / Q000378:metabolism; D012867:Skin / Q000187:drug effects* / Q000378:metabolism*; D015595:Skin Aging; D013472:Sunlight; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D024042:Collagen Type I; D024061:Collagen Type III; C416830:GREB1 protein, human; D009363:Neoplasm Proteins; D011347:Procollagen; D011960:Receptors, Estrogen; D004958:Estradiol