Emerging targets of the GnRH receptor: novel interactions with Wnt signalling mediators

The diversity of signalling pathways that gonadotropin-releasing hormone (GnRH) receptors can target has been extended markedly in recent years, ranging from classical heterotrimeric G-protein-coupled second-messenger mobilisation to MAPK cascade activation and epidermal growth factor receptor transactivation. More recently, the targeting of non-classical signalling pathways has been demonstrated, including the activation of monomeric G-proteins and integrin/focal adhesion complexes to mediate cytoskeletal remodelling, androgen receptor nuclear translocation, and luteinising hormone beta-subunit gene transcription. These have been further extended to include c-Src-mediated activation of diacylglycerol kinase, and a novel mechanism of cross-talk to prostaglandin receptor signalling. Here, we review these recent advances and highlight several emerging dimensions in GnRH receptor-mediated signal transduction. These include the targeting of mediators of classical insulin signalling, and Wnt signalling pathways. Collectively, this diverse nature of GnRH receptor signalling is suggestive of an important role for GnRH in a variety of normal physiological and pathophysiological processes in the reproductive system.