Abstract
In order to clarify the physiological function of fibroblast growth factor (FGF-2) in the adrenal medulla the regulation of FGF-2 and FGF receptor 1 (FGFR1) was studied in vitro and in vivo in response to glucocorticoids. To assess the effects of glucocorticoids, in vivo extracts of adrenal medulla and adrenal cortex were analyzed by RNase protection assay and Western blot analysis. PC12 cells were chosen as a model system to study the effects of glucocorticoids in vitro. In PC12 cells, dexamethasone (DEX) was found to stimulate dramatically the expression of both FGF-2 mRNA and protein. Western blot analysis revealed that exclusively the 21-kDa FGF-2 isoform was enhanced. In contrast to the FGF-2 mRNA level FGFR1 was not affected by treatment with glucocorticoids. In vivo FGF-2 mRNA level and 21-kDa FGF-2 isoform level are significantly enhanced in the adrenal medulla 24 h after DEX injection. In vivo application of DEX leads to an increase of the medullary and cortical FGFR1 transcript levels. Glucocorticoid effects on FGF-2 expression were not found in adrenal cortex, heart, skeletal muscle, and kidney, respectively, in vivo and in L6 rat myoblasts in vitro. In addition to adrenal medullary cells glucocorticoids elevated the FGF-2 mRNA and protein level also in vivo in the brain and in vitro in immortalized Schwann cells. The present results suggest that the 21-kDa FGF-2 isoform mediates a physiological function specific for neuronal tissue which is modulated by glucocorticoids.
Highlights
FGFs are known to mediate cellular effects via cell surface receptor tyrosine kinases (FGF receptors, FGFRs)
The present results suggest that the 21-kDa FGF-2 isoform mediates a physiological function specific for neuronal tissue which is modulated by glucocorticoids
The present results show that GCs enhance FGF-2 protein and mRNA in PC12 cells in vitro and in adrenal medullary cells in vivo
Summary
FGFs are known to mediate cellular effects via cell surface receptor tyrosine kinases (FGF receptors, FGFRs). Low affinity receptors have been characterized as cell surface hepacortex, heart, skeletal muscle, and kidney, respectively, ran sulfate proteoglycans, e.g. the integral membrane proteoin vivo and in L6 rat myoblasts in vitro. In addition to adrenal medullary cells glucocorticoids FGFR4 are found in extracts of the adrenal gland [17, 18]. In elevated the FGF-2 mRNA and protein level in vivo the adrenal cortex of the embryonic mouse the FGFR4 mRNA in the brain and in vitro in immortalized Schwann cells. Adrenal gland FGFR1 transcript is present in preparations of the cortex and medulla [20]. FGF-2 mRNA and protein are present in several regions of the embryonic, postnatal, and adult central nervous system [5,6,7]. Nerve growth factor (NGF) induces a significant increase of FGFR1 mRNA in PC12 cells under serumcontaining culture conditions suggesting that NGF enhances the responsivity to FGF [20]
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