Effect of estrogen on cellular metabolism of the human anterior cruciate ligament

Clin Orthop Relat Res. 1999 Sep;(366):229-38. doi: 10.1097/00003086-199909000-00030.


Previous studies from this laboratory have established the presence of estrogen receptors in the human anterior cruciate ligament. The purpose of this study was to investigate the effects of 17 beta-estradiol on cell proliferation and procollagen levels, as an indicator of collagen synthesis, in the human anterior cruciate ligament fibroblasts. Fibroblast proliferation and procollagen synthesis in response to near log concentrations of 17 beta-estradiol (at 0.0029 ng/mL, 0.025 ng/mL, 0.25 ng/mL, 2.5 ng/mL, and 25 ng/mL) were assessed with the measurement of 3H-thymidine incorporation and Types 1 and 3 procollagen specific equilibrium radioimmunoassays. On Days 1 and 3, there was a dose dependent decrease in the proliferation of anterior cruciate ligament fibroblasts with increasing estradiol concentrations. This dose dependent effect of decreased fibroblast proliferation with increasing estradiol concentrations became less apparent at 7, 10, and 14 days. On Days 1 and 3, procollagen synthesis decreased in a dose dependent manner with increasing estradiol concentrations. On Days 7, 10, and 14, this dose dependent effect was attenuated. No significant differences in Type 3 procollagen synthesis by anterior cruciate ligament fibroblasts were observed with varying estradiol concentrations at any of the designated points. These early physiologic changes in fibroblast proliferation and Type I procollagen synthesis may provide a biologic explanation for the increased anterior cruciate ligament injury rate observed in female athletes, suggesting that it is the acute cyclic variations in the female athlete who is menstruating that predisposes her to ligamentous injury.

MeSH terms

  • Adult
  • Anterior Cruciate Ligament / cytology
  • Anterior Cruciate Ligament / drug effects*
  • Anterior Cruciate Ligament / metabolism
  • Anterior Cruciate Ligament Injuries
  • Athletic Injuries / etiology
  • Blotting, Western
  • Cell Division / drug effects
  • Cells, Cultured
  • Collagen / biosynthesis
  • Collagen / drug effects
  • Dose-Response Relationship, Drug
  • Estradiol / administration & dosage
  • Estradiol / pharmacology*
  • Female
  • Fibroblasts / cytology
  • Fibroblasts / drug effects
  • Humans
  • Linear Models
  • Menstruation / physiology
  • Procollagen / analysis
  • Procollagen / drug effects
  • Radiopharmaceuticals
  • Receptors, Estrogen / metabolism
  • Risk Factors
  • Thymidine / metabolism
  • Time Factors
  • Tritium


  • Procollagen
  • Radiopharmaceuticals
  • Receptors, Estrogen
  • Tritium
  • Estradiol
  • Collagen
  • Thymidine