Kisspeptin: past, present, and prologue

Research in the nineteenth and early twentieth century established that the brain awakens reproduction, governs reproductive activity in the adult of virtually all vertebrates. By 1950, nearly 100 years later, scientists realized that the hypothalamus and its neurosecretory products play a key role in regulating gonadal function in both males and females. Another 20 years would be required to reveal the chemical identity of GnRH and establish that neurons producing GnRH represent the final common pathway through which the brain regulates gonadotropin secretion. It had also become clear that GnRH neurons behave more like motor neurons-better perhaps at going than stopping-and are themselves regulated by a complex network of afferent inputs, which guide the tempo of sexual maturation, regulate estrous and menstrual cycles, control seasonal breeding, and stop reproduction under adversity. In 2003, the revelation that kisspeptin and its receptor are critical for reproduction opened a floodgate of research documenting the role of kisspeptin neurons as central processors of reproduction. Today, there is wide consensus that kisspeptin signaling in the brain is essential, providing the impetus to GnRH neurons to awaken at puberty and reigning the activity of these neurons when discretion is advised. We celebrate this watershed moment-with full knowledge that time and discovery will provide context and perspective to even these heady days.