Specific involvement of glycogen synthase kinase-3 in the function and activity of sex steroid hormone receptors reveals the complexity of their regulation

Protein kinases represent key nodes for the integration of multiple intracellular signalling pathways, resulting in modulation of both ligand-dependent and ligand-independent mechanisms of sex steroid receptor (sSR) signalling cascades. The proline-directed Ser/Thr kinases including mitogen-activated protein kinases and cyclin dependent kinases were especially reported to contribute to the function and activity of sSRs. The relevant effects of these kinases are well-documented but the impact of glycogen synthase kinase-3 (GSK-3), another member of this kinase family, has been underestimated. Indeed, the specific role of GSK-3 regarding the different sSRs will help to understand further the complexity of sSR signalling. So far, AR and ERα were identified as GSK-3 substrates. Additionally, the docking properties of GSK-3 were demonstrated to play a crucial role in sSR signal transduction. Reciprocally, GSK-3 was described as a potential target of non-genomic effects of sSRs. Therefore, GSK-3 regulates and is regulated by sSRs. This review focuses on the emerging and promising involvements of GSK-3 regarding the signalling cascade of the respective sSRs. This review represents a necessary complement of information to highlight the importance of GSK-3 regarding sSR function and activity.