The roles of kisspeptin and gonadotropin inhibitory hormone in stress-induced reproductive disorders.

Several kinds of stress suppress the hypothalamic-pituitary-gonadal (HPG) axis and reproductive behavior in humans and animals. These changes can eventually cause diseases and disorders, such as amenorrhea and infertility. In previous studies, it has been shown that stress-related factors, e.g., corticotropin-releasing hormone, cortisol, and pro-inflammatory cytokines, promote the stress-induced suppression of the HPG axis. However, these mechanisms are not sufficient to explain how stress suppresses HPG axis activity, and it has been suggested that some other factors might also be involved. In the early 21st century, novel neuroendocrine peptides, kisspeptin and gonadotropin inhibitory hormone (GnIH)/RFamide-related peptide 3 (RFRP-3), which directly regulate GnRH/gonadotropin synthesis and secretion, were newly discovered. Growing evidence indicates that kisspeptin and GnIH/RFRP-3 play pivotal roles in the stress-induced disruption of the HPG axis and reproductive behavior in addition to their physiological functions. This review summarizes what is currently known about the roles of kisspeptin and GnIH/RFRP-3 in stress-induced reproductive disorders.