Prolonged and intense stress chronically increases blood concentration of glucocorticoids, which in turn causes downregulation of glucocorticoid receptor (GR) in the central nervous system (CNS). This process has been suggested to be involved in the pathogenesis of major depressive disorder (MDD). Here, we found that basic fibroblast growth factor (bFGF) increased the expression of GR in the rat cerebral cortex and cultured cortical neurons and restored the reduced GR expression caused by glucocorticoid exposure. Among intracellular signaling pathways stimulated by bFGF, extracellular signal–regulated kinase/mitogen-activated protein kinase (ERK/MAPK) pathway was responsible for the upregulation of GR. The bFGF-induced GR was functional as a transcription factor to enhance transcription of a target gene. Because high stress augments bFGF levels in the brain, it is likely that bFGF plays a compensating role for reduced GR expression after stress and thus should be studied as a therapeutic target for the treatment of MDD.

长期而紧张的压力会长期增加糖皮质激素的血药浓度，进而导致中枢神经系统（CNS）中糖皮质激素受体（GR）的下调。已经表明该过程与重度抑郁症（MDD）的发病机理有关。在这里，我们发现碱性成纤维细胞生长因子（bFGF）增加了大鼠大脑皮层和培养的皮质神经元中GR的表达，并恢复了糖皮质激素暴露引起的GR表达降低。在bFGF刺激的细胞内信号传导途径中，细胞外信号调节激酶/促分裂原活化蛋白激酶（ERK / MAPK）途径是GR上调的原因。bFGF诱导的GR是转录因子，可增强靶基因的转录。