Central mechanisms of action of kisspeptin-10 in stress-induced reproductive dysfunction

Background: Emotional stress impairs both mental and reproductive health, being accompanied by hormonal dysregulation that is difficult to correct. Kisspeptin is a neuropeptide that regulates the reproductive system through its effects on hypothalamic–pituitary mechanisms. Although the incidence of stress-induced reproductive disorders is increasing, effective approaches targeting the central components of neuroendocrine regulation remain limited. The role of kisspeptin in restoring the hypothalamic–pituitary–gonadal axis under chronic stress has not been sufficiently studied, creating a significant gap in the understanding of pathogenesis and the potential for its pharmacological correction.

Aim: The work aimed to investigate the effect of kisspeptin-10 on the activity of the kisspeptin–gonadotropin-releasing hormone system in male rats (Rattus norvegicus) in a model of posttraumatic stress disorder.

Methods: The study included 42 Wistar rats, which were divided into 7 groups and exposed to restraint stress or vital stress. Kisspeptin-10 was administered intranasally or intraperitoneally. The levels of selected neuropeptides and their receptors in the hypothalamus and amygdala were assessed using enzyme-linked immunosorbent assay.

Results: Kisspeptin-10 increased the levels of gonadotropin-releasing hormone, kisspeptin, and the kisspeptin receptor in the brain. An activating effect on androgen receptor expression was observed, predominantly in the hypothalamus.

Conclusions: The findings indicate a central mechanism of action of kisspeptin-10 that is independent of sex steroids and demonstrate its potential in the treatment of stress-induced reproductive dysfunction.