The female reproductive function largely depends on timing and coordination between follicle-stimulating hormone (FSH) and luteinizing hormone (LH). Even though it was suggested that these hormones act on granulosa cells via shared signalling pathways, mainly protein kinases A, B, and C (PKA, PKB, PKC), there is still very little information available on how these signalling pathways are regulated by each hormone to provide such differences in gene expression throughout folliculogenesis. To obtain a global picture of the principal upstream factors involved in PKA, PKB, and PKC signalling in granulosa cells, human granulosa-like tumour cells (KGN) were treated with FSH or specific activators (forskolin, SC79, PMA) for each pathway to analyze gene expression with RNA seq technology. Normalization and cut-offs (FC 1.5, p ≤ 0.05) revealed 3,864 differentially expressed genes between treatments. Analysis of major upstream regulators showed that PKA is a master kinase of early cell differentiation as its activation resulted in the gene expression profile that accompanies granulosa cell differentiation. Our data also revealed that the activation of PKC in granulosa cells is also a strong differentiation signal that could control "advanced" differentiation in granulosa cells and the inflammatory cascade that occurs in the dominant follicle. According to our results, PKB activation provides support for PKA-stimulated gene expression and is also involved in granulosa cell survival throughout follicular development. Taken together, our results provide new information on PKA, PKB, and PKC signalling pathways and their roles in stimulating a follicle at the crossroad between maturation/ovulation and atresia.

中文翻译：

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人卵巢颗粒肿瘤细胞 (KGN)† 中受促性腺激素调节的主要信号通路的基因分析。

女性生殖功能很大程度上取决于促卵泡激素 (FSH) 和促黄体生成素 (LH) 之间的时间和协调。尽管有人建议这些激素通过共享的信号通路作用于颗粒细胞，主要是蛋白激酶 A、B 和 C（PKA、PKB、PKC），但关于这些信号通路如何被每个细胞调节的信息仍然很少。激素在整个卵泡发生过程中提供基因表达的这种差异。为了全面了解参与颗粒细胞中 PKA、PKB 和 PKC 信号传导的主要上游因素，人类颗粒样肿瘤细胞 (KGN) 用 FSH 或特定激活剂（forskolin、SC79、PMA）处理，以达到使用 RNA seq 技术分析基因表达。归一化和临界值 (FC 1.5, p ≤ 0.05) 显示 3，864 个处理间差异表达的基因。对主要上游调节因子的分析表明，PKA 是早期细胞分化的主要激酶，因为它的激活导致伴随颗粒细胞分化的基因表达谱。我们的数据还显示，颗粒细胞中 PKC 的激活也是一种强分化信号，可以控制颗粒细胞的“高级”分化和优势卵泡中发生的炎症级联反应。根据我们的结果，PKB 激活为 PKA 刺激的基因表达提供支持，并且还参与整个卵泡发育过程中的颗粒细胞存活。总之，我们的结果提供了关于 PKA、PKB、