| Summary: | 碩士 === 國立成功大學 === 生理學研究所 === 90 === Fibroblast growth factor-9 (FGF-9) is a potent mitogen and survival factor for numerous nerve cells and prostatic cells. However, the significance of FGF-9 in female reproductive tract has not been investigated. The objective of this study is to examine the role of FGF-9 in human uterine endometrium. My results show that FGF-9 is expressed at high level in normal uterine endometrium, especially during the late proliferative phase, which is coincident with the rise of estradiol and the time of uterine endometrium proliferation. Using RT-PCR analysis, I found that FGF-9 was produced primarily by endometrial stromal cells. High affinity receptors of FGF-9 were detected in both epithelial and stromal cells with distinct patterns. FGFR2IIIc and FGFR3IIIc were the most abundant isoforms in endometrial stromal cells. FGFR2IIIb was markedly expressed in endometrial epithelial cells whereas FGFR3IIIb was found in both epithelial and stromal cells. Treatment with FGF-9 induced endometrial stromal proliferation in a dose-dependent manner but had no substantial effect on epithelial cells. In accordance with this this result, cyclin D1 and cyclin A were induced by thetreatment with FGF-9 in stromal cells. Using selective protein kinase inhibitors demonstrated that FGF-9 induced cell proliferation was mediated via phosphatidylinositol 3-kinase and mitogen-activated protein kinase signaling pathways. Treatment of stromal cells with 17��-estrodiol stimulated FGF-9 expression and cell proliferation. Furthermore, the mitogenic effect of estrogen was inhibited by co-treatment with anti-FGF-9 antibody. In conclusion, the results of my study have demonstrated, for the first time, that FGF-9 is an autocrine estromedin endometrial stromal growth factor that plays significant roles in cyclic proliferation of uterine endometrium.
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