Expression and mitogenic effect of fibroblast growth factor-9 in human endometriotic implant is regulated by aberrant production of estrogen.
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.
Wing
Lih-Yuh C
LY
Department of Physiology, National Cheng Kung University Medical College, Tainan 701, Taiwan, Republic of China.
Chuang
Pei-Chin
PC
Wu
Meng-Hsing
MH
Chen
Hsiu-Mei
HM
Tsai
Shaw-Jenq
SJ
D002455:Cell Division / Q000187:drug effects; D016889:Endometrial Neoplasms; D004715:Endometriosis / Q000378:metabolism / Q000503:physiopathology*; D004958:Estradiol / Q000096:biosynthesis* / Q000494:pharmacology; D005260:Female; D051525:Fibroblast Growth Factor 9; D005346:Fibroblast Growth Factors / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D008598:Menstruation / Q000502:physiology; D008934:Mitogens / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D011388:Prolactin / Q000096:biosynthesis; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics; D017154:Stromal Cells / Q000166:cytology; D014407:Tumor Cells, Cultured
C496459:FGF9 protein, human; D051525:Fibroblast Growth Factor 9; D008934:Mitogens; D017468:Receptors, Fibroblast Growth Factor; D004958:Estradiol; D005346:Fibroblast Growth Factors; D011388:Prolactin