Anania C A, Stewart E A, Quade B J, Hill J A, Nowak R A
Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Mol Hum Reprod. 1997 Aug;3(8):685-91. doi: 10.1093/molehr/3.8.685.
Basic fibroblast growth factor (bFGF) is a regulator of angiogenesis which is overexpressed in leiomyomas compared with matched myometrium. To understand the physiological significance of this finding we characterized the expression of the type 1 receptor for this ligand (FGFR1). Utilizing reverse transcription-polymerase chain reaction (RT-PCR) we identified the complete and alternatively spliced transmembrane forms and two secreted forms of the FGFR1 in endometrium, myometrium and leiomyomas from all patients. This is the first report of secreted forms in uterine tissue. Proteins consistent with each of these isoforms were identified by Western blot analysis in all three tissues. Immunohistochemistry revealed menstrual cycle-specific regulation of FGFR1 protein in the endometrial stroma of normal women but not in women with leiomyomas and abnormal uterine bleeding. Stromal FGFR1 expression is suppressed in the early luteal phase in normal women, but not in women with leiomyoma-related bleeding. These findings support the role of the bFGF ligand-receptor system in the pathogenesis of leiomyoma-related bleeding and may have implications for fertility and contraception since the differential FGFR1 expression occurs in the peri-implantation period of the early luteal phase.
碱性成纤维细胞生长因子（bFGF）是血管生成的调节因子，与配对的子宫肌层相比，其在平滑肌瘤中过度表达。为了理解这一发现的生理学意义，我们对该配体的1型受体（FGFR1）的表达进行了表征。利用逆转录-聚合酶链反应（RT-PCR），我们在所有患者的子宫内膜、子宫肌层和平滑肌瘤中鉴定出了FGFR1的完整和选择性剪接的跨膜形式以及两种分泌形式。这是子宫组织中分泌形式的首次报道。通过蛋白质印迹分析在所有三种组织中鉴定出了与这些异构体一致的蛋白质。免疫组织化学显示，正常女性子宫内膜基质中FGFR1蛋白存在月经周期特异性调节，但平滑肌瘤和子宫异常出血的女性中则没有。正常女性在黄体早期基质FGFR1表达受到抑制，但平滑肌瘤相关出血的女性中则没有。这些发现支持了bFGF配体-受体系统在平滑肌瘤相关出血发病机制中的作用，并且可能对生育和避孕有影响，因为FGFR1的差异表达发生在黄体早期的植入前期。
