Magnaghi V, Riva M A, Cavarretta I, Martini L, Melcangi R C
Department of Endocrinology, Institute of Pharmacological Sciences, University of Milan, Italy.
J Mol Neurosci. 2000 Aug;15(1):11-8. doi: 10.1385/JMN:15:1:11.
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.
目前的数据表明，在大鼠1型星形胶质细胞中，FGF-1和FGF-2的基因表达受皮质类固醇调节。特别是，FGF-1的基因表达受作用于I型（盐皮质激素）和II型（糖皮质激素）受体的皮质类固醇调节。事实上，在短时间暴露（2小时）时，脱氧皮质酮（一种能与I型受体相互作用的类固醇）可诱导FGF-1 mRNA水平略有下降；在暴露于皮质酮或其5α-还原代谢物二氢皮质酮6小时后也观察到类似效果。相反，在较长时间暴露（24小时）时，皮质酮能够强烈增加FGF-1 mRNA水平。地塞米松重复了皮质酮的两种作用（抑制和刺激），表明这两种作用均通过II型受体发生。有趣的是，脱氧皮质酮的5α-3α-还原代谢物四氢脱氧皮质酮不与任何一种皮质类固醇受体相互作用，但能够（在暴露6小时和24小时时）刺激FGF-1的基因表达。这种作用可能是通过GABAA受体诱导的，因为该受体的激动剂蝇蕈醇也有类似作用。FGF-2的情况有所不同。这种生长因子的mRNA水平仅受与II型受体相互作用的类固醇刺激。总之，这些观察结果表明，皮质类固醇通过与经典（I型和II型）或非经典（GABAA受体）类固醇受体相互作用来调节星形胶质细胞中FGF-1和FGF-2基因表达的水平。
