Hormones and growth factors induce the synthesis of glial fibrillary acidic protein in rat brain astrocytes

Abstract

Glial fibrillary acidic protein (GFAP) is the major constituent of glial filaments and is restricted within the CNS to astrocytes. As with other classes of intermediate filament proteins, the regulation of GFAP expression is poorly understood. Utilizing highly purified cultures of astrocytes and a chemically defined (CD) medium, we have demonstrated that the expression of GFAP is subject to regulation by hormones and growth factors. The concentration of GFAP/mg protein was induced 2-4-fold in the presence of hydrocortisone, putrescine, prostaglandin F-2 alpha (PGF2 alpha), and pituitary fibroblast growth factor (FGF). Augmentation of the levels of GFAP continued for up to 3 weeks after conversion to CD medium and paralleled the morphological maturation of astrocytes. The accumulation of GFAP resulted from an increase in its specific rate of synthesis. Conversion of astrocytes from serum-supplemented (SS) to CD medium did not alter its rate of degradation. GFAP appeared quite stable under both sets of conditions, exhibiting a half-life of approximately 7.5 days. The data demonstrate that GFAP expression in astrocytes is subject to hormonal regulation, which may have implications for gliosis.

Basic Fibroblast Growth Factor Ameliorates Rotational Behavior of Substantia Nigral-Transplanted Rats with Lesions of the Dopaminergic Nigrostriatal Neurons.

“…Reports have indicated that bFGF induces morpholo gical changes in astrocyte cells both in vitro and in vivo (14,28). In this study, staining with anti-GFAP anti body showed stronger gliosis in the grafted regions in the 50 ng bFGF-treated group as compared with the control and 5 ng bFGF-treated rats (Fig.…”

“…Although the relation between induction of gliosis and improve ment of neuronal survival has not been clarified exact ly, the dense gliosis induced by a high dose of bFGF (50 ng) presumably results in less grafted neuron survi val and less amelioration of abnormal rotations. Besides the morphological alteration of glial cells, bFGF induced other responses in glial cells, such as proliferation (29), glial fibrillary protein synthesis (28), nerve growth factor release (30), glutamine synthase synthesis (31) and protein kinase activation (32). Among these bFGF-induced multiple responses, there may be an ability to stimulate dopaminergic neurons, e.g., by release of a dopaminotrophic factor, but this effect has not yet been identified.…”

Gene expression of cyclooxygenase-1 and Ca2+-independent phospholipase A2 is altered in rat hippocampus during normal aging

“…The same tendency was observed for PGE 2 levels, although it did not reach statistical significance. Prostaglandins have been shown to have numerous effect on astrocytes in vitro including upregulating GFAP expression [31]. Thus, it should be further clarified if the astrocytic activation observed during aging is either the consequence or the cause of altered AA metabolism.…”

Characterization of Glucocorticoid Type II Receptors in Neuronal and Glial Cultures from Rat Brain

“…Ample evidence also suggests that glia serve as targets for these hormones. For example, glucocorticoids can induce glycerol phosphate dehydrogenase and glutamine synthetase activity (12,18,33,(47)(48)(49), change cell shape and microfilament contents (50,51) and suppress cell growth (52). Since glucocorticoids such as CORT and DEX also bind to mineralocorticoid Type I receptors with high affinity (24), questions concerning which type of receptor mediates glucocorticoid-induced responses on specific cell types are difficult to study in vivo.…”