Journal of Molecular Neuroscience 11 Volume 15, 2000 Corticosteroids Regulate the Gene Expression of FGF-1 and FGF-2 in Cultured Rat Astrocytes V. Magnaghi, 1 M. A. Riva, 2 I. Cavarretta, 1 L. Martini, 1 and R. C. Melcangi* ,1 1 Department of Endocrinology and 2 Center of Neuropharmacology, Institute of Pharmacological Sciences, University of Milan Via G. Balzaretti 9, Milan 20133, Italy Abstract The present data show that the gene expression of FGF-1 and FGF-2 is regulated by corti- costeroids in rat type 1 astrocytes. In particular, the gene expression of FGF-1 is modulated by corticosteroids acting both on type I (minerocorticoid) and type II (glucocorticoid) receptors. In fact, at short times of exposure (2 h) a slight decrease in FGF-1 mRNA levels is induced by deoxycorticosterone, a steroid able to interact with the type I receptors; a similar effect is observed at 6 h following exposure to corticosterone or its 5 -reduced metabolite, dihydrocorticosterone. Conversely, at longer times of exposure (24 h) corticosterone is able to strongly increase FGF-1 mRNA levels. Both effects of corticosterone (inhibition and stimulation) were duplicated by dexamethasone, indicating that both effects occur via the type II receptors. Interestingly, the 5 -3 -reduced metabolite of deoxycorticosterone, tetrahydrodeoxycorticosterone, which does not interact with either corticosteroid receptors, is able to stimulate (at 6 and 24 h of exposure) the gene expression of FGF-1. It is possible that this effect might be induced via the GABA A receptor, since muscimol, an agonist of this receptor, exerts a similar effect. The situation is different in the case of FGF-2. The mRNA levels of this growth factor are only stimulated by steroids interacting with type II receptors. Altogether, these observations indicate that corticosteroids modulate the levels of FGF-1 and FGF-2 gene expression in astroglial cells by interaction with classical (type I and II) or nonclassical (GABA A receptor) steroid receptors. Key Words: Corticosterone; 5 - and 5 -3 -reduced metabolites; type I and II corticosteroid receptors; FGF-1; FGF-2; GABA A receptor; astrocytes. *Author to whom all correspondence and reprint requests should be addressed. E-mail: melcangi@mailserver.unimi.it Journal of Molecular Neuroscience Copyright © 2000 Humana Press Inc. All rights of any nature whatsoever reserved. ISSN0895-8696/00/15:-11–18/$12.00