NCBI Summary:
The protein encoded by this gene is a member of the fibroblast growth factor (FGF) family. FGF family members possess broad mitogenic and cell survival activities, and are involved in a variety of biological processes, including embryonic development, cell growth, morphogenesis, tissue repair, tumor growth and invasion. This protein functions as a modifier of endothelial cell migration and proliferation, as well as an angiogenic factor. It acts as a mitogen for a variety of mesoderm- and neuroectoderm-derived cells in vitro, thus is thought to be involved in organogenesis. Multiple alternatively spliced variants encoding different isoforms have been described. [provided by RefSeq, Jan 2009]
Effects of fibroblast growth factors and the transcription factor, early growth response 1, on bovine theca cells. Han P et al. (2018) The theca cell layer of the ovarian follicle secretes growth factors that impact the function of granulosa cells. One such factor is fibroblast growth factor 18 (FGF18) that causes apoptosis of granulosa cells, however it is not known if FGF18 induces apoptosis also in theca cells. Addition of recombinant FGF18 to bovine theca cells in vitro inhibited steroidogenesis but, in contrast to previous data in granulosa cells, decreased the incidence of apoptosis. FGF18 activated typical FGF signaling pathways in theca cells, which was not previously observed in granulosa cells. The transcription factor Early Growth Response-1 (EGR1) was a target of FGF18 action; overexpression and knock-down experiments demonstrated that EGR1 is a major upstream component of FGF signaling in theca cells and that it directs cell fate toward proliferation. These data suggest that FGF18 is mitogenic for theca cells while being pro-apoptotic in granulosa cells.//////////////////
Do the Theca Layer and Fibroblast Growth Factors Have a Role in Follicular Atresia? Armstrong DT et al. The hypothesis that FGFs of theca cell origin regulate bovine follicular atresia in vivo is discussed in the context of FGF interactions with extracellular heparan sulfate glycosaminoglycans which can limit their availability to granulosa cell receptors.
SNT1/FRS2 mediates germinal vesicle breakdown induced by an activated FGF receptor1 in Xenopus oocytes.
Mood K, et al .
The docking protein SNT1/FRS2 (fibroblast growth factor receptor substrate 2) is implicated in the transmission of extracellular signals from the fibroblast growth factor receptor (FGFR), which plays vital roles during embryogenesis. Activating FGFR mutations cause several craniosynostoses and dwarfism syndromes in humans. Here we show that the Xenopus homolog of mammalian FRS-2 (XFRS2) is essential for the induction of oocyte maturation by an XFGFR1 harboring an activating mutation (XFGFR1act). Using a dominant-negative form of kinase suppressor of Ras, we show the Mek activity is required for germinal vesicle breakdown (GVBD) induced by co-expression of XFGFR1act and XFRS2, but this activity is not required for progesterone-induced GVBD. Furthermore, Mek/MAPK activity is critical for the induction and/or maintenance of H1 kinase activity at metaphase of meiosis II in progesterone-treated oocytes. An activated XFGFR1 containing a mutation in the phospholipase Cgamma binding site (XFGFR1actY672F) displayed a reduced ability to induce cell-cycle progression in oocytes, suggesting phospholipase Cgamma may not be necessary but that it augments XFGFR signaling in this system. Oocytes co-expressing XFGFR1act and XFRS2 showed substantial H1 kinase activity, but this activity was blocked when the oocytes were treated with the phosphatidylinositol 3-kinase inhibitor LY294002. Although phosphatidylinositol 3-kinase activity is essential for XFGFR1act/XFRS2-induced oocyte maturation, this activity is not required for maturation induced by progesterone. Finally, ectopic expression of Xspry2, a negative regulator of XFGFR signaling, greatly reduced MAPK activation and GVBD induced by the expression of either XFGFR1act plus XFRS2 or activated Ras (H-RasV12). In contrast, Xspry2 did not prevent GVBD induced by an activated form of Raf1, suggesting that Xspry2 exerts its inhibitory function upstream or parallel to Raf and downstream of Ras.
Expression regulated by
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Ovarian localization
Theca
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Berisha B, et al reported the expression and localization of fibroblast growth factor (FGF) family members during the final growth of bovine ovarian follicles.
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The aim of this study was to investigate the possible participation of fibroblast growth factor (FGF) family members: FGF1, FGF2, and FGF7, and their receptor variants: FGFR, FGFR2IIIb, and FGFR2IIIc in theca interna (TI) and granulosa cell (GC) compartments of bovine follicles during final growth. A classification of follicles into five groups (<0.5; >0.5-5; >5-20; >20-180; >180 ng/ml, respectively) was performed according to the follicular fluid (FF) oestradiol-17beta (E) content. The mRNA expression and protein localization was analyzed by reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry. FGF1 mRNA expression was relatively high in TI and lower in GC, and without any regulatory change for both tissue compartments during final follicular growth. The FGF1 protein could be predominantly localized in the cytoplasm of GC, in smooth muscle cells of blood vessels, in the rete ovarii, and at a lesser degree in theca cells. FGF2 mRNA in TI increased significantly in large follicles and was low and without any regulatory change in GC. FGF7 mRNA expression was relatively high in TI and very low in GC. For FGF7 in mature follicles a marked staining of the TI and the basal layers of the GC could be demonstrated. The mRNA signal for the FGFR in TI increased significantly with beginning of E production (E > 0.5-5 ng/ml FF) and was without any regulatory change in GC. The mRNA expression of FGFR2IIIb was relatively high in GC and increased significantly during final growth of follicles in contrast to the TI with very low expression. The FGFR2IIIc mRNA expression in TI and GC was relatively high but without any clear change. Our results suggest that FGF growth factor family members are involved in process of folliculogenesis and especially during final growth of the preovulatory (dominant) follicle by stimulation of angiogenesis and GC survival and proliferation.
Follicle stages
Antral, Preovulatory, Corpus luteum
Comment
Expression of Fibroblast Growth Factor 1 (FGF1) and FGF7 in Mature Follicles during the Periovulatory Period after GnRH in the Cow Berisha B, e al .
The aim of this study was to evaluate the expression pattern of mRNA for fibroblast growth factor 1 (FGF1), FGF7, and their receptor variants (FGFR2IIIb) in time-defined follicle classes before LH surge, between LH surge and ovulation, and in the early corpus luteum (CL) in the cow. The ovaries were collected by transvaginal ovariectomy (n=5 cows/group), and the follicles (n=5, one follicle/cow) were classified into the following groups: before GnRH administration (before LH surge); 3-5 h after GnRH (during LH surge); 10 h after GnRH; 20 h after GnRH; 25 h after GnRH (periovulation), and early CL (Days 2-3). The mRNA expression was analyzed by quantitative real-time PCR (RotorGene 3000). The mRNA expression of FGF1 showed no significant differences in the follicle groups examined, but increased significantly at the early CL phase. A transient increase in FGF7 mRNA expression was observed 3-5 h after GnRH and again in the early CL phase. In contrast, the expression of FGFR2IIIb was constant throughout the period from the final growth of the follicle to early CL formation. The results of this study suggest that FGF1 and FGF7 may be involved differently in the process of follicle maturation and CL formation, which is strongly dependent on angiogenesis.