Corticosteroids regulate the gene expression of FGF-1 and FGF-2 in cultured rat astrocytes.
The present data show that the gene expression of FGF-1 and FGF-2 is regulated by corticosteroids 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 5alpha-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 5alpha-3alpha-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.
Magnaghi
V
V
Department of Endocrinology, Institute of Pharmacological Sciences, University of Milan, Italy. melcangi@mailserver.unimi.it
Riva
M A
MA
Cavarretta
I
I
Martini
L
L
Melcangi
R C
RC
D000305:Adrenal Cortex Hormones / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D016220:Fibroblast Growth Factor 1; D016222:Fibroblast Growth Factor 2 / Q000235:genetics*; D018755:GABA Agonists / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000502:physiology; D009118:Muscimol / Q000494:pharmacology; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000187:drug effects / Q000378:metabolism
D000305:Adrenal Cortex Hormones; D018755:GABA Agonists; D012333:RNA, Messenger; D011963:Receptors, GABA-A; D011965:Receptors, Glucocorticoid; D016222:Fibroblast Growth Factor 2; D016220:Fibroblast Growth Factor 1; D009118:Muscimol