We are exploring the pathways of progesterone signaling, an unconventional mechanism that adjusts pain thresholds in the nervous system, as well as regulates sperm activation and egg maturation in the reproductive tissues. Progesterone, a hormone produced by the cells that surround an egg, attracts sperm to their target and activates them once they arrive. In the nervous system, progesterone can elevate the pain threshold and exerts analgesic action. Using a technique that I perfected while at UCSF, I determined that progesterone promotes the entry of calcium through channels in the sperm cell membrane-- an event so central for fertilization that men lacking these channels are infertile. I will identify how progesterone binds to its targets and determine how this molecular coupling ultimately regulates the crucial calcium channels in sperm and pain sensing neurons. These findings could lead to the development of new diagnostics or treatments for male infertility, could help develop safe male contraceptives, as well as devise novel strategies to manage pain.