Expression and mitogenic effect of fibroblast growth factor-9 in human endometriotic implant is regulated by aberrant production of estrogen

J Clin Endocrinol Metab. 2003 Nov;88(11):5547-54. doi: 10.1210/jc.2003-030597.

Abstract

Fibroblast growth factor-9 (FGF-9) is a steroid-regulated mitogen and survival factor for nerve and mesenchymal cells. In the current study, we determined the expression pattern and functional roles of FGF-9 in the ectopic endometriotic lesions. We found that FGF-9 and its receptors were effectively expressed by ectopic endometriotic tissues. The expression of FGF-9 was greater in the early stage of endometriosis, compared with the severe stage, which is consistent with concentration of 17 beta-estradiol in the peritoneal fluid of women with endometriosis. In addition, expression of FGF-9 in ectopic endometriotic stromal cell was inhibited by treatment with ICI 182,870 indicating it is likely regulated by estrogen in an autocrine manner. Administration of 17 beta-estradiol induced FGF-9, FGF receptor 2IIIc, and FGF receptor 3IIIc expression in endometriotic stromal cells. Concordant with this result, treatment of endometriotic stromal cells with 4-hydroxyandrostenedione (an aromatase inhibitor) or ICI 182,870 inhibited their proliferation, and that was reversed by coadministration with 17 beta-estradiol or FGF-9. In conclusion, expression of FGF-9 in endometriotic stromal cells is associated with aberrant production of estrogen. The capability of proliferation possessed by endometriotic stromal cell during menstruation when ovarian 17 beta-estradiol is in the nadir may be mediated, at least in part, by autocrined estrogen-stimulated expression of FGF-9 and its receptors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Division / drug effects
  • Endometrial Neoplasms
  • Endometriosis / metabolism
  • Endometriosis / physiopathology*
  • Estradiol / biosynthesis*
  • Estradiol / pharmacology
  • Female
  • Fibroblast Growth Factor 9
  • Fibroblast Growth Factors / genetics*
  • Fibroblast Growth Factors / metabolism
  • Fibroblast Growth Factors / pharmacology
  • Gene Expression / drug effects
  • Humans
  • Menstruation / physiology
  • Mitogens / genetics*
  • Mitogens / metabolism
  • Mitogens / pharmacology
  • Prolactin / biosynthesis
  • Receptors, Fibroblast Growth Factor / genetics
  • Stromal Cells / cytology
  • Tumor Cells, Cultured

Substances

  • FGF9 protein, human
  • Fibroblast Growth Factor 9
  • Mitogens
  • Receptors, Fibroblast Growth Factor
  • Estradiol
  • Fibroblast Growth Factors
  • Prolactin