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Fibroblast Growth Factor-9 Is an Endometrial Stromal Growth Factor

Departments of Physiology (S.-J.T., H.-M.C., P.-C.C., L.-Y.W.) and Obstetrics & Gynecology (M.-H.W.), National Cheng Kung University Medical College, Tainan 70101, Taiwan, Republic of China

Address all correspondence and requests for reprints to: Lih-Yuh C. Wing, Ph.D., Department of Physiology, National Cheng Kung University Medical College, Tainan, Taiwan, Republic of China. E-mail: . wing{at}mail.ncku.edu.tw

Fibroblast growth factor-9 (FGF-9) is an autocrine/paracrine growth factor considered to be important for the growth and survival of motorneurons and prostate. In this study, we found that FGF-9 was expressed at high levels in normal uterine endometrium, especially during the late proliferative phase, which is coincident with the rise of estradiol and the time of uterine endometrial proliferation. Using quantitative RT-PCR analysis, we found that FGF-9 mRNA was expressed primarily by endometrial stromal cells. High affinity receptors of FGF-9 were detected in both epithelial and stromal cells but with distinct patterns. FGFR2IIIc and FGFR3IIIc are abundant in endometrial stromal cell. FGFR2IIIb is mostly expressed in endometrial epithelial cells, whereas FGFR3IIIb is found in both epithelial and stromal cells. Treatment with FGF-9 induces endometrial stromal proliferation in a dose-dependent manner. Expression of FGF-9 in stromal cells was induced by 17ß-estradiol but not by progesterone. Furthermore, the administration of 17ß-estradiol stimulates endometrial stromal cell proliferation and that can be inhibited by cotreatment with anti-FGF-9 antibody. Herein we demonstrate, for the first time, that FGF-9 is an autocrine estromedin endometrial stromal growth factor that plays roles in cyclic proliferation of uterine endometrial stroma.

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