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At least 667 records · Page 37Linked to original sources
PubMed1996

Basic fibroblast growth factor (FGF-2) affects development of acoustico-vestibular neurons in the chick embryo brain in vitro.

The effects of basic fibroblast growth factor (FGF-2) on presumptive auditory and vestibular neurons from the medulla were studied in primary cell cultures. The part of the rhombic lip that forms nucleus magnocellularis (homologue of the mammalian anteroventral cochlear nucleus) was explanted from white leghorn chicken embryos at Hamburger-Hamilton stage 28 (E5.5), the time when precursors of the magnocellularis bushy cells migrate and begin to differentiate in situ. In vitro the neuroblasts migrated onto 2-D substrates of purified collagen, differentiated, and expressed neuronal markers. One-half of the cultures were supplemented with human recombinant FGF-2 (10 ng/ml daily) for 5-7 days; the others, with fetal bovine serum. FGF-2 more than doubled the length of neurite outgrowth during the first 3 day treatment compared to serum, but the number of migrating neuroblasts was unaffected. Although neurites attained greater lengths in FGF-2, they usually degenerated after 4-5 days; in serum their growth continued for several weeks. Differentiation of neuronal structure, including axons and dendrites, began within 1-2 days in bFGF but required at least 5-7 days in serum. Histochemical observations in vitro and in situ with antibodies to FGF receptor demonstrated immunopositive patches on acoustico-vestibular neuroblasts at stage 28, when they are migrating and first forming their axons. The findings suggest that FGF-2 stimulates neurite outgrowth in the cochlear and vestibular nuclei. FGF-2 may accelerate cell death by overstimulating neuroblasts, but other factors are needed to sustain their further development.

Analysis of Variance↗
PubMed1999

FGF-9 is an autocrine/paracrine neurotrophic substance for spinal motoneurons.

Motoneurons need muscle-derived neurotrophic substances for their survival during the initial phase of their development, but after maturation they lose this requirement and can survive after axotomy. This suggests that some neurotrophic substances other than target-derived ones control the survival of motoneurons in adults. Because spinal motoneurons express fibroblast growth factor-9 (FGF-9) messenger RNA, we hypothesized that FGF-9 might be an autocrine or paracrine survival factor for motoneurons. FGF-9 promoted the survival of motoneurons and upregulated the choline acetyl-transferase (ChAT) activity in the dissociated cultures of ventral half of rat E13 spinal cord. Externally added FGF-9 was more effective in low density cultures, and polyclonal blocking antibody against FGF-9 significantly lowered the ChAT activity. Our results support an autocrine or paracrine role for FGF-9 in mediating the survival of spinal motoneurons. Non-target-derived neurotrophic substances for motoneurons including FGF-9 should be important in the pathogenesis of motor neuron disorders in the adults, especially amyotrophic lateral sclerosis.

Animals↗
PubMed2000

Multiple functions of fibroblast growth factor-8 (FGF-8) in chick eye development.

Fibroblast growth factor-8 (FGF-8) is an important signaling molecule in the generation and patterning of the midbrain, tooth, and limb. In this study we show that it is also involved in eye development. In the chick, Fgf-8 transcripts first appear in the distal optic vesicle when it contacts the head ectoderm. Subsequently Fgf-8 expression increases and becomes localized to the central area of the presumptive neural retina (NR) only. Application of FGF-8 has two main effects on the eye. First, it converts presumptive retinal pigment epithelium (RPE) into NR. This is apparent by the failure to express Bmp-7 and Mitf (a marker gene for the RPE) in the outer layer of the optic cup, coupled with the induction of NR genes, such as Rx, Sgx-1 and Fgf-8 itself. The induced retina displays the typical multilayered cytoarchitecture and expresses late neuronal differentiation markers such as synaptotagmin and islet-1. The second effect of FGF-8 exposure is the induction of both lens formation and lens fiber differentiation. This is apparent by the expression of a lens specific marker, L-Maf, and by morphological changes of lens cells. These results suggest that FGF-8 plays a role in the initiation and differentiation of neural retina and lens.

Animals↗
PubMed2000

FGF-8 stimulates neuronal differentiation through FGFR-4a and interferes with mesoderm induction in Xenopus embryos.

The role of fibroblast growth factors (FGFs) in neural induction is controversial [1,2]. Although FGF signalling has been implicated in early neural induction [3-5], a late role for FGFs in neural development is not well established. Indeed, it is thought that FGFs induce a precursor cell fate but are not able to induce neuronal differentiation or late neural markers [6-8]. It is also not known whether the same or distinct FGFs and FGF receptors (FGFRs) mediate the effects on mesoderm and neural development. We report that Xenopus embryos expressing ectopic FGF-8 develop an abundance of ectopic neurons that extend to the ventral, non-neural, ectoderm, but show no ectopic or enhanced notochord or somitic markers. FGF-8 inhibited the expression of an early mesoderm marker, Xbra, in contrast to eFGF, which induced ectopic Xbra robustly and neuronal differentiation weakly. The effect of FGF-8 on neurogenesis was blocked by dominant-negative FGFR-4a (DeltaXFGFR-4a). Endogenous neurogenesis was also blocked by DeltaXFGFR-4a and less efficiently by dominant-negative FGFR-1 (XFD), suggesting that it depends preferentially on signalling through FGFR-4a. The results suggest that FGF-8 and FGFR-4a signalling promotes neurogenesis and, unlike other FGFs, FGF-8 interferes with mesoderm induction. Thus, different FGFs show specificity for mesoderm induction versus neurogenesis and this may be mediated, at least in part, by the use of distinct receptors.

Animals↗
PubMed2002

The role of the anterior neural ridge and Fgf-8 in early forebrain patterning and regionalization in Xenopus laevis.

The tissue, cellular and molecular mechanisms that regulate early regional specification of the vertebrate forebrain are largely unknown. We studied the expression patterns of Xbf-1, an anterior (and telencephalon) neural-specific winged helix transcription factor and Fgf-8, an early-secreted factor. This study looked at Xbf-1 and Fgf-8 expression in combination with embryonic grafting experiments and also used beads containing the recombinant Fgf-8 protein to determine these factors' effects upon forebrain patterning events. We provide evidence that additional Fgf-8 displaces Xbf-1 expression posteriorly, suggesting a concentration dependence of Fgf-8 for the early distinct regionalization of the telencephalic primordia. Also, additional stage 15 mid-anterior neural ridge (mANR) transplants inhibited telencephalon development, whereas lateral ANR transplants facilitated increased areas of telencephalon development. In both cases, these transplantations promoted ectopic expression of Xbf-1. These studies suggested that the distinct regionalization of the forebrain primordia involves the inhibitory actions of the mANR towards a telencephalon development and maintaining bilateral telencephali. These telencephalic primordia are initially localized by optimal Fgf-8 expression. The anterior mANR will eventually become the anterior and rostral diencephalic tissue. This in vivo study demonstrated Fgf-8 and the mANR are important in forebrain regionalization.

Animals↗
PubMed2002

Smooth muscle cell proliferation induced by oxidized LDL-borne lysophosphatidylcholine. Evidence for FGF-2 release from cells not extracellular matrix.

Oxidized low-density lipoprotein (oxLDL), which accumulates in vascular lesions, alters vascular cell function in ways that can be construed as atherogenic. Among these is the observation that oxLDL and its lipids promote smooth muscle cell (SMC) proliferation. A number of schemes have been proposed to explain this phenomenon. Our published data support the concept that part of the proliferation is mediated by lysophosphatidylcholine (lysoPC) and structurally related phospholipids borne by oxLDL, which cause FGF-2 release via an oxidant-dependent mechanism. Since FGF-2 can bind extracellular matrices, we wanted to determine whether the FGF-2 released came from an intracellular or an extracellular matrix-bound pool. We tested whether lysoPC was capable of releasing FGF-2 from SMC matrices, whether agents that release FGF-2 from matrices could cause proliferation, and whether lysoPC-mediated proliferation could occur by stimulating metalloproteinase (MMP)-induced matrix degradation, which released matrix-bound FGF-2. Our results indicate that the source of FGF-2 released by lysoPC and related lipids is a preexisting cellular pool and not from matrix, and that the mechanism likely involves transient, sublethal cell permeabilization. These results enhance understanding of a mechanism by which oxLDL could contribute to SMC proliferation in arterial lesions.

Animals↗
PubMed2004

Kinetic model for FGF, FGFR, and proteoglycan signal transduction complex assembly.

The current working model for fibroblast growth factor receptor (FGFR) dimerization and activation requires the assembly of a ternary complex of fibroblast growth factor (FGF), FGFR, and heparin or heparan sulfate proteoglycan (HSPG) on the plasma membrane. The recent FGF2-FGFR1-heparin crystal structure provides a detailed but static view of the FGF-FGFR-heparin complex. However, the kinetics of ternary complex assembly has yet to be investigated. Here, we characterize FGF2, FGFR1, and heparin interactions using surface plasmon resonance (SPR). Binding constants for binary FGF2/FGFR1 (KD = 62 nM), FGF2/heparin (KD = 39 nM), and FGFR1/heparin (KD = 3.2 microM) interactions correlate to the magnitude of binding interface observed in the FGF2-FGFR1-heparin crystal structure. Interestingly, comparison of sensorgrams of sequential injections of FGF2 and FGFR1 and equimolar FGF2-FGFR1 injections onto a heparin neoproteoglycan surface demonstrates that FGF2 dramatically enhances the association of FGFR1 with heparin and leads us to propose a model for the stepwise assembly of a ternary FGF-FGFR-HSPG complex. The weak binding affinity of the FGFR1-heparin interaction suggests that in this model, FGFR and HSPG are unbound in the absence of FGF ligand. The availability of FGF results in formation of initial FGF-HSPG complexes, which promotes the rapid binding of FGFR and creates a ternary complex capable of undergoing dimerization and subsequent FGFR activation. In contrast, alternative models for the kinetic assembly of a ternary complex in which binary FGF-FGFR or FGFR-HSPG complexes are intermediates do not conform well with the experimental data.

Dimerization↗
PubMed2005

Molecular mechanism of inhibition of nonclassical FGF-1 export.

Fibroblast growth factor (FGF-1) lacks a signal sequence and is exported by an unconventional release mechanism. The nonclassical export of FGF-1 has been shown to be inhibited by an anti-allergic and anti-inflammatory drug, amlexanox (AMX). We investigate the molecular mechanism(s) underlying the inhibitory action of AMX on the release of FGF-1, using a variety of biophysical techniques including multidimensional NMR spectroscopy. AMX binds to FGF-1 and enhances its conformational stability. AMX binds to locations close to Cys30 and sterically blocks Cu(2+)-induced oxidation, leading to the formation of the homodimer of FGF-1. AMX-induced inhibition of the formation of the FGF-1 homodimer is observed both under cell-free conditions and in living cells. Results of this study suggest a novel approach for the design of drugs against FGF-1-mediated disorders.

Aminopyridines↗
PubMed2006

Structural requirements of FGF-1 for receptor binding and translocation into cells.

FGF-1 binds to and activates specific transmembrane receptors (FGFRs) and is subsequently internalized and translocated to the interior of the cell. To elucidate the role of the receptor in the translocation process, we studied the effects of the elimination of distinct sites of the ligand-receptor interaction. On the basis of the structure of the FGF-1-FGFR1 complex, we substituted four key amino acid residues of FGF-1 from the FGF-receptor binding site with alanines, constructing four point mutants and one double mutant. We determined by in vivo assays in NIH 3T3 cells the ability of the mutants to bind to specific FGF receptors, to stimulate DNA synthesis, and to activate downstream signaling pathways. We found that correct binding to the receptor is necessary for optimal stimulation of DNA synthesis. All four single mutants became phosphorylated to different extents, indicating that they were translocated to the cytosol/nucleus with varying efficiency. This indicates that despite a low affinity for FGFR, translocation to the cytosol/nucleus can still occur. However, simultaneous substitution in two of the positions led to a total loss of biological activity of the growth factor and prevented its internalization, implying that there is only one strongly receptor-dependent, productive way of translocating FGF-1. We also found that the process of translocation did not correlate with the thermal stability of the protein. Additionally, we observed a clear negative correlation between the stability of the FGF-1 mutants and the efficiency of their phosphorylation, which strongly suggests that protein kinases prefer the unfolded state of the protein substrate.

Amino Acid Substitution↗
PubMed1996

Two hierarchies of FGF-2 signaling in heparin: mitogenic stimulation and high-affinity binding/receptor transphosphorylation.

FGF-2 activates multiple signaling pathways by a cell surface signaling complex assembled with FGF, its receptor tyrosine kinase, and heparan sulfate proteoglycan. Heparan sulfate binds to a site on the receptor and at least one site on the growth factor. Several models propose an important role for heparan sulfate not only in facilitating FGF-2 binding to its receptor tyrosine kinase but also in promoting signaling via formation of receptor dimers. Such dimers are capable of transphosphorylation of the cytoplasmic domain of the receptor, leading to the generation of phosphotyrosines that are important initiators of intracellular signaling pathways. To explore the participation of heparan sulfates in the formation of a signaling complex that activates these pathways, the binding and activity of FGF-2 on Swiss 3T3 fibroblasts and F32 lymphoid cells is examined with either native or modified forms of heparin. As shown previously, fibroblasts treated with chlorate, which inhibits the sulfation of heparan sulfate and its subsequent binding to FGF-2, display a dramatically reduced response to picomolar concentrations of FGF-2, but binding to receptors and a mitogenic response is restored by heparin. However, the restoration of high-affinity binding is seen only at an optimal concentration of heparin. Excess heparin competes for binding sites within the signaling complex such that high-affinity binding and receptor transphosphorylation are reduced. Despite this, mitogenic signaling is not diminished. A similar result is observed using heparin fragments that promote mitogenesis but not high-affinity binding. These results suggest that the high-affinity signaling complex that is necessary for stable receptor transphosphorylation differs from the signaling complex sufficient for triggering mitogenesis. We speculate that heparan sulfate in vivo participates in two hierarchies of receptor activation. In one, heparan sulfate participates in FGF-2 binding to its receptor tyrosine kinase and activation of mitogenic signaling, perhaps through monomeric receptors or the transient formation of receptor dimers. In the second hierarchy, heparan sulfate participates in the stabilization of a signaling complex that is likely to be comprised of receptor multimers that carry out effective receptor transphosphorylation. A further description of this mechanism may lead to an understanding of how heparan sulfate or its homologues can regulate specific signaling pathways within the cell.

3T3 Cells↗
PubMed1997

Endothelial cells overexpressing basic fibroblast growth factor (FGF-2) induce vascular tumors in immunodeficient mice.

Basic fibroblast growth factor (FGF-2) is expressed in vascular endothelium during tumor neovascularization and angioproliferative diseases, including vascular tumors and Kaposi's sarcoma (KS). We have investigated the in vivo biological consequences of endothelial cell activation by endogenous FGF-2 in a mouse aortic endothelial cell line transfected with a retroviral expression vector harboring a human FGF-2 cDNA and the neomycin resistance gene. FGF-2 transfectants, named pZipbFGF2-MAE cells, caused the rapid growth of highly vascularized, non-infiltrating tumors when injected in nude mice. In contrast, lesions grew poorly when cells were injected in immunocompetent syngeneic animals. Histologically, the tumors had the appearance of hemangioendothelioma with spindled areas resembling KS and with numerous CD31+ blood vessels and lacunae. Southern blot analysis of tumor DNA, as well as disaggregation of the lesion followed by in vitro cell culture, revealed that less than 10% of the cells in the tumor mass retain FGF-2 overexpression and neomycin resistance at 6-8 weeks post-injection. Nevertheless, in vitro G418 selection allowed the isolation from the tumor of a FGF-2-overexpressing cell population showing biochemical and biological characteristics similar to those of pZipbFGF2-MAE cells, including the capacity to originate vascular lesions when re-injected in nude mice. To evaluate the effect of angiostatic compounds on the growth and vascularization of pZipbFGF2-MAE cell-induced lesions, nude mice were treated weekly (100mg/kg, i.p.) with the angiostatic sulfonated distamycin A derivative 2,2'-(carbonyl-bis-[imino-N-methyl-4,2-pyrrole carbonyl-imino-{N-methyl-4,2-pyrrole}carbonylimino])-bis-(1,5-naphthalene) disulfonic acid (PNU 153429). The results demonstrate that PNU 153429 inhibits the growth of the lesions and causes a approximately 50% decrease in CD31+ microvessel density. In conclusion, the data indicate that FGF-2-overexpressing endothelial cells cause vascular lesions in immunodeficient mice which may represent a novel model for opportunistic vascular tumors suitable for the evaluation of angiostatic compounds.

Journal Article↗
PubMed2003

Cell-based and direct gene transfer-induced angiogenesis via a secreted chimeric fibroblast growth factor-1 (sp-FGF-1) in the chick chorioallantoic membrane (CAM).

Fibroblast growth factor-1 (FGF-1) is a potent angiogenic factor; its structure lacks a signal peptide for secretion. We previously reported that the overexpression of a secreted version of FGF-1 (sp-FGF-1) in microvascular endothelial cells (ECs) enhances cell migration [Partridge et al. J Cell Biochem 2000; 78(3): 487]. In the current study, we have examined the angiogenic effects of sp-FGF-1 in chicken chorioallantoic membranes (CAMs). Two methods of examining the effects of sp-FGF-1 in CAMs were used: cell-mediated transfection via bovine ECs and direct gene transfection. In the cell-mediated gene transfection, those eggs that were implanted with a gelatin sponge seeded with ECs stably transfected to over-express sp-FGF-1 protein showed a significant increase in angiogenesis inside the sponge when compared to eggs treated with vector control-transfected ECs. In the direct gene transfer, eggs received sp-FGF-1 showed a significant increase in vascularization when compared to eggs received vector alone plasmids. These CAM models are useful both for studying molecular mechanisms of angiogenesis and for developing better gene therapy strategies.

Allantois↗
PubMed1993

First experience with FGF-3 (INT-2) amplification in women with epithelial ovarian cancer.

Estimation of FGF-3 oncogene amplification in DNA samples extracted from paraffin embedded sections of 136 ovarian cancer samples was carried out by a quantitative PCR method. The aim of this study was to elucidate a possible association of FGF-3 copy numbers with established prognostic factors such as age, histology, FIGO stage, grading, postoperative residual tumour mass, ascites, hormone receptor content and preoperative CA 125 serum levels. In addition, correlation of FGF-3 amplification with overall survival of the patients was assessed. There was a borderline positive correlation between preoperative CA 125 serum levels and the degree of amplification of the FGF-3 gene (P = 0.06). A statistically significant association of FIGO-stage with FGF-3 copy number could be found (P = 0.008). No correlation between FGF-3 amplification and overall survival was noted. The data combine to suggest that FGF-3 is an indicator of aggressiveness of ovarian cancer.

Actuarial Analysis↗
PubMed1998

The activation and composition of FiRE (an FGF-inducible response element) differ in a cell type- and growth factor-specific manner.

The expression of the heparan sulfate proteoglycan, syndecan-1, is induced both in keratinocytes and in fibroblasts during development and tissue regeneration. Here we report that in keratinocytes the syndecan-1 gene was stimulated by EGF but not by FGF-2. In fibroblasts it was stimulated by FGF-2 but not by EGF. Likewise, the recently discovered FGF-inducible response element (FiRE) on the gene of syndecan-1 was stimulated by FGF-2 in fibroblasts and by EGF in keratinocytes, but not vice versa. The FiRE has two binding sites for an activator protein-1 (AP-1), one for an FGF-inducible nuclear factor (FIN-1) and one for an upstream stimulatory factor-1 (USF-1). The growth factor-stimulated binding of these transcription factors, as well as their requirement for FiRE activation, varied between the two cell types. First, although AP-1s were required for activation of FiRE in both cell types, the binding of AP-1 to FiRE was increased by growth factor-stimulation only in fibroblasts and not in keratinocytes. Secondly, FiRE did not bind FIN-1 nor needed the FIN-1 binding site for EGF-stimulated activation in keratinocytes, in contrast to the FGF-stimulated activation of FiRE in fibroblasts. Thirdly, EGF, which did not activate FiRE in fibroblasts, failed to activate FIN-1 in these cells. Finally, an USF-1 binding site that was necessary for activation of FiRE in keratinocytes was not needed in fibroblasts. These data suggest mechanisms by which members of the EGF- and FGF-families can differentially stimulate transcription through AP-1 regulated elements in a cell type-specific manner.

3T3 Cells↗
PubMed1999

Functional Rac-1 and Nck signaling networks are required for FGF-2-induced DNA synthesis in MCF-7 cells.

The effects of Fibroblast Growth Factor-2 (FGF-2) on breast cancer cell DNA synthesis are controversial. To elucidate the mechanisms by which FGF-2 stimulates or inhibits DNA synthesis, we analysed FGF-2 signaling pathways in breast cancer MCF-7 and MCF-7 cells overexpressing Ha-Ras (MCF-7ras). We found that FGF-2-induction of DNA synthesis correlates with Ras transient activation, FRS-2 tyrosine phosphorylation and low level of expression of p66Shc. In addition, Nck-associated proteins are highly tyrosine phosphorylated and JNK reaches a higher level of activation when FGF-2 triggers DNA synthesis. Interestingly upon FGF-2 treatment, JNK activation and DNA synthesis are dependent on Rac-1 activity. These results confirm that in MCF-7 cells, induction of DNA synthesis by FGF-2 requires a transient activation of the Ras/MAPK cascade and demonstrates for the first time that intact Rac-1 and Nck signaling networks are required.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Role of the FGF and MEK signaling pathway in the ascidian embryo.

In the ascidian embryo, a fibroblast growth factor (FGF)-like signal from presumptive endoderm blastomeres between the 32-cell and early 64-cell stages induces the formation of notochord and mesenchyme cells. However, it has not been known whether endogenous FGF signaling is involved in the process. Here it is shown that 64-cell embryos exhibit a marked increase in endogenous extracellular signal-regulated kinase (ERK/MAPK) activity. The increase in ERK activity was reduced by treatment with an FGF receptor 1 inhibitor, SU5402, and a MEK (ERK kinase/MAPKK) inhibitor, U0126. Both drugs blocked the formation of notochord and mesenchyme when embryos were treated at the 32-cell stage, but not at the 2- or 110-cell stages. The dominant-negative form of Ras also suppressed notochord and mesenchyme formation. Both inhibitors suppressed induction by exogenous basic FGF. These results suggest that the FGF signaling cascade is indeed necessary for the formation of notochord and mesenchyme cells during ascidian embryogenesis. It is also shown that FGF signaling is required for formation of the secondary notochord, secondary muscle and neural tissues, and at least ERK activity is necessary for the formation of trunk lateral cells and posterior endoderm. Therefore, FGF and MEK signaling are required for the formation of various tissues in the ascidian embryo.

Animals↗
PubMed2002

Neuroprotection by scatter factor/hepatocyte growth factor and FGF-1 in cerebellar granule neurons is phosphatidylinositol 3-kinase/akt-dependent and MAPK/CREB-independent.

Neuroprotective actions of scatter factor/hepatocyte growth factor (SF/HGF) have not been described. We examined the effects of SF/HGF in comparison to acidic fibroblast growth factor-1 (FGF-1) on N-methyl-D-aspartate (NMDA) and quinolinic acid (QUIN)-induced excitotoxicity in primary cerebellar granule neurons. Exposure to NMDA or QUIN for 24 h resulted in concentration-dependent cell death (p < 0.001) that was completely attenuated (p < 0.001) by pre-treatment of cells with SF/HGF (50 ng/mL) or FGF-1 (40 ng/mL). SF/ HGF and FGF-1 activated both Akt and MAP-kinase > threefold (p < 0.001). Neither SF/HGF nor FGF-1 activated cyclic AMP-response element binding protein (CREB), a downstream target of MAP-kinase, whereas brain-derived neurotrophic factor (BDNF) activated both MAP-kinase and CREB in granule neurons. Neuroprotection against NMDA or QUIN by SF/HGF and FGF-1 was negated by the addition of LY294002 (10 microM) or wortmannin (100 microM), two distinct inhibitors of phosphatidylinositol 3-kinase (P13-K), but not by the MAP-kinase kinase (MEK) inhibitor PD98059 (33 microm). Likewise, expression of a dominant-negative mutant of Akt (Akt-kd) completely prevented the neuroprotective actions of SF/HGF and FGF-1. Overexpression of a constitutively activated Akt (Akt-myr) or wild-type Akt (wtAkt) attenuated excitotoxic cell death. These data show that both SF/HGF and FGF-1 protect cerebellar granule neurons against excitotoxicity with similar potency in a P13-K/Akt-dependent and MAP-kinase/CREB-independent manner.

Animals↗
PubMed1995

Fasting increases the expression of basic fibroblast growth factor (FGF-2) messenger ribonucleic acid in rat hypothalamus.

Basic fibroblast growth factor (FGF-2) has been isolated from the brain, but the regulation of FGF-2 synthesis in the brain is not yet fully understood. Since exogenously administered FGF-2 has been reported to suppress food intake as well as the secretion of gastric acid and pepsin in rats, we examined the effect of fasting on FGF-2 mRNA levels in the hypothalamus and the cerebral cortex of male rats, using RNase protection assay. Fasting for 72 h resulted in an approximately 2-fold increase in FGF-2 mRNA level in the hypothalamus but did not affect FGF-2 mRNA level in the cerebral cortex significantly. These findings support the hypothesis that FGF-2 plays a significant role in regulation of hypothalamic function.

Adrenalectomy↗