Multiple effects of kisspeptin on neuroendocrine, reproduction, and metabolism in polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is a highly prevalent and heterogeneous disease characterized by a combination of reproductive and endocrine abnormalities, often associated with metabolic and mental health disorders. The etiology and pathogenesis of PCOS remain unclear, but recent research has increasingly focused on the upstream mechanisms underlying its development. Among these, kisspeptin (KISS) signaling has emerged as a pivotal component in the regulation of the hypothalamic-pituitary-gonadal axis, with significant roles in reproductive function, energy regulation, and metabolism. Women with PCOS commonly exhibit disruptions in gonadotropin secretion, including elevated luteinizing hormone (LH) levels, imbalanced LH/follicle-stimulating hormone (FSH) ratios, and increased androgen levels, all of which are usually parallel with abnormal KISS signaling. Furthermore, alterations in the KISS/KISS1R system within the central and circulatory systems, as well as peripheral tissues, have been implicated in the development of PCOS. These changes affect multiple pathophysiological domains, including reproductive function, energy regulation, metabolic homeostasis, inflammatory response, and emotional disorders, and are further influenced by lifestyle and environmental factors. This review aims to comprehensively summarize the existing experimental and clinical evidence supporting these roles of KISS in PCOS, with the goal of establishing a foundation for future research and potential clinical applications.