- Publication date : 2020-05-19
Patricia G. Tremblay, Marc-André Sirard Gene Analysis of Major Signalling Pathways Regulated by Gonadotropins in Human Ovarian Granulosa Tumour Cells (KGN)† 2020 May 19;ioaa079. doi: 10.1093/biolre/ioaa079. Online ahead of print. DOI: 10.1093/biolre/ioaa079
granulosa cells ovary
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.