Stress regulation of kisspeptin in the modulation of reproductive function

Stressful stimuli abound in modern society and have shaped evolution through altering reproductive development, behavior, and physiology. The recent identification of kisspeptin as an important component of the hypothalamic regulatory circuits involved in reproductive homeostasis sparked a great deal of research interest that subsequently implicated kisspeptin signaling in the relay of metabolic, environmental, and physiological cues to the hypothalamo-pituitary-gonadal axis. However, although it is widely recognized that exposure to stress profoundly impacts on reproductive function, the roles of kisspeptin within the complex mechanisms underlying stress regulation of reproduction remain poorly understood. We and others have recently demonstrated that a variety of experimental stress paradigms downregulate the expression of kisspeptin ligand and receptor within the reproductive brain. Coincidently, these stressors also inhibit gonadotropin secretion and delay pubertal onset-processes that rely on kisspeptin signaling. However, a modest literature is inconsistent with an exclusively suppressive influence of stress on the reproductive axis and suggests that complicated neural interactions and signaling mechanisms translate the stress response into reproductive perturbations. The purpose of this chapter is to review the evidence for a novel role of kisspeptin signaling in the modulation of reproductive function by stress and to broaden the understanding of this timely phenomenon.