Kisspeptin: Bridging physiology and clinical application in HPG axis regulation

Abstract

Kisspeptin (Kp), a neuropeptide primarily produced by neuronal clusters within discrete hypothalamic nuclei from the KISS1 gene, serves as a critical initiator of puberty and regulator of ovulation in sexually mature females through central control of the hypothalamic-pituitary-gonadal (HPG) axis. Its interaction with the G protein-coupled receptor (GPR) 54 is indispensable for activating the HPG axis. Although extensively studied in various animal models including rodents, primates, and livestock such as sheep and cattle, the physiological characterization of the KISS1R/GPR54 system remains ongoing. Evidence suggests that KISS-1 neurons occupy a central role in the regulation of the gonadotropinreleasing hormone (GnRH) system. Beyond reproduction, Kp expression influences non-reproductive functions such as lactation, stress response, nutrition, cancer, and metabolism. The development of agonists and antagonists targeting KISS1R/GPR54 holds promise for therapeutic advancements. This paper provides a comprehensive review of Kp, its physiological effects, and the responses to its analogs on reproductive functions in animals, highlighting its importance for therapeutic and diagnostic interventions in animal reproductive diseases and infertility.