College of Animal Science and Technology, Northwestern A&F University, Yangling, ShaanXi, China.
Reproduction. 2012 Nov;144(5):625-32. doi: 10.1530/REP-12-0199. Epub 2012 Sep 6.
Several fibroblast growth factors (FGFs), including FGF1, FGF4 and FGF10, alter ovarian granulosa cell function. These ligands exhibit different patterns of receptor activation, and their mechanisms of action on granulosa cells remain unknown. The objective of this study was to identify the major pathways and target genes activated by FGF1, FGF4 and FGF10 in primary oestrogenic granulosa cells cultured under serum-free conditions. FGF1 and FGF4 increased levels of mRNA encoding Sprouty family members, SPRY2 and SPRY4, and the orphan nuclear receptors NR4A1 and NR4A3. Both FGF1 and FGF4 decreased levels of mRNA encoding SPRY3 and the pro-apoptotic factor BAX. FGF1 but not FGF4 stimulated expression of the cell cycle regulator, GADD45B. In contrast, FGF10 altered the expression of none of these genes. Western blot demonstrated that FGF4 activated ERK1/2 and Akt signalling rapidly and transiently, whereas FGF10 elicited a modest and delayed activation of ERK1/2. These data show that FGF1 and FGF4 activate typical FGF signalling pathways in granulosa cells, whereas FGF10 activates atypical pathways.
几种成纤维细胞生长因子（FGFs），包括 FGF1、FGF4 和 FGF10，可改变卵巢颗粒细胞的功能。这些配体表现出不同的受体激活模式，其对颗粒细胞的作用机制尚不清楚。本研究的目的是鉴定在无血清条件下培养的原代雌激素性颗粒细胞中，FGF1、FGF4 和 FGF10 激活的主要途径和靶基因。FGF1 和 FGF4 增加了编码 Sprouty 家族成员 SPRY2 和 SPRY4 以及孤儿核受体 NR4A1 和 NR4A3 的 mRNA 水平。FGF1 和 FGF4 均降低了编码 SPRY3 和促凋亡因子 BAX 的 mRNA 水平。FGF1 但不是 FGF4 刺激了细胞周期调节剂 GADD45B 的表达。相比之下，FGF10 没有改变这些基因的表达。Western blot 表明，FGF4 迅速且短暂地激活 ERK1/2 和 Akt 信号通路，而 FGF10 则适度且延迟地激活 ERK1/2。这些数据表明，FGF1 和 FGF4 在颗粒细胞中激活了典型的 FGF 信号通路，而 FGF10 则激活了非典型的信号通路。
