表皮生长因子对卵巢激活素基因表达的调节及其信号通路

背景：激活素作为卵巢内调控分子,对卵巢卵泡发育起着重要作用。 目的：探索表皮生长因子在激活素基因表达过程中所起的重要作用以及可能参与调节的信号通路。 方法：分离斑马鱼卵巢卵泡,体外培养6 d,消化后传代培养24 h。表皮生长因子单独或与其他分子抑制剂(AG1478、H89、GF109203X)或激动剂(FK、PMA)联合处理细胞,提取细胞RNA,反转录PCR检测细胞激活素表达量。 结果与结论：表皮生长因子可快速提高激活素表达量,其作用可能是通过磷酸化信号分子丝裂原活化蛋白激酶实现,而蛋白激酶C特异性抑制剂或激动剂可减弱或加强表皮生长因子对丝裂原活化蛋白激酶信号分子的激活,显示卵巢内激活素表达受表皮生长因子调节,蛋白激酶C/丝裂原活化蛋白激酶信号通路参与了这种调节作用。蛋白激酶A抑制剂也能抑制表皮生长因子对激活素表达的促进作用。

Regulation of activin gene expression by epidermal growth factor and its signal pathway in the ovary

BACKGROUND:As a regulator in the ovary, activin plays an important role in the development of ovarian follicle. OBJECTIVE:To explore effects of epidermal growth factor (EGF) on activin gene expression and the signal pathway participating in regulation. METHODS:The follicles were separated from ovaries of zebra fish and cultured in vitro for 6 days. After digestion, cells were subcultured for 24 hours. The cells were treated with EGF alone, or combined with pharmacological inhibitor (AG1478, H89, GF109203X) or activator (Forskolin, PMA). Cell RNA was extracted. The expression of activin βA was detected by RT-PCR. RESULTS AND CONCLUSION:EGF rapidly increased activin βA expression, and phosphorylation of two mitogen activated protein kinases (MAPKs) was enhanced by EGF. A specific pharmacological inhibitor or activator of protein kinase C (PKC) decreased or increased the stimulation of EGF on MAPKs phosphorylation. These results demonstrate that activins working as intraovarian regulatory moleculars modulate the follicular development in ovary, its expression is regulated by EGF, PKC/MAPKs signal pathway involved in the regulation on activin βA expression. Protein kinase A inhibitor can suppress the promoting effect of EGF on activin expression.