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Expression and Mitogenic Effect of Fibroblast Growth Factor-9 in Human Endometriotic Implant Is Regulated by Aberrant Production of Estrogen

Department of Physiology (L.-Y.C.W., H.-M.C., S.-J.T.), Institute of Basic Medical Sciences (P.-C.C., S.-J.T.), and Institute of Clinical Medicine and Department of Obstetrics/Gynecology (M.-H.W.), National Cheng Kung University Medical College, Tainan 701, Taiwan, Republic of China

Address all correspondence and requests for reprints to: Shaw-Jenq Tsai, Ph.D., Department of Physiology, National Cheng Kung University Medical College, 1 University Road, Tainan 701, Taiwan, Republic of China. E-mail: seantsai{at}mail.ncku.edu.tw.

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 17ß-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 17ß-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 17ß-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 17ß-estradiol is in the nadir may be mediated, at least in part, by autocrined estrogen-stimulated expression of FGF-9 and its receptors.

This work was supported by a grant from the National Science Council of Taiwan (NSC91-2320-B-006-061).

Abbreviations: E₂, 17ß-Estradiol; EGF, epidermal growth factor; ER, estrogen receptor; FBS, fetal bovine serum; FGF, fibroblast growth factor; FGFR, FGF receptor; GAPDH, glyceraldehyde 3-phosphate dehydrogenase; 4-HA, 4-hydroxyandrostenedione; PRL, prolactin; QC-RT-PCR, quantitative, competitive RT-PCR; StAR, steroidogenic acute regulatory protein.

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