Potential Clinical Use of Kisspeptin

Abstract

Over the last 10 years, kisspeptins - peptide products of varying lengths encoded by the KISS1 gene - have been found to be key regulators of normal reproductive function throughout life in animals and humans. By activating the kisspeptin receptor [previously known as orphan G protein-coupled receptor 54 (GPR54)], they elicit an effect on the central gonadotropin-releasing hormone neurons. Administration of kisspeptin by either the subcutaneous or intravenous route potently stimulates endogenous gonadotropin hormone release in healthy men and women as well as in animals. Kisspeptin also stimulates endogenous release of gonadotropins in subfertile as well as healthy volunteers, and therefore it has potential as a novel therapeutic agent in reproductive disorders. Further human studies have shown that chronic, high-dose administration of kisspeptin causes desensitisation with rapid subsequent suppression of the hypothalamic-pituitary-gonadal axis, and therefore high-dose long-acting analogues may have a clinical role in treating sex hormone-dependent malignancies. By further elucidating the intricacies and mechanisms of the kisspeptin signalling system, and the tissues it acts on during different phases of the reproductive timeline (including during puberty, fertility, pregnancy and menopause), pharmacologic analogues could become clinically useful.

Kisspeptin serum levels in acute myocardial infarction patients and healthy individuals

“…In a study conducted by Jayasena et al, on the effect of kisspeptin on miscarriage, smoking by pregnant women was demonstrated to not have a significant relationship with kisspeptin serum levels (Prague and Dhillo, 2015), which is consistent with the present study.…”

“…Since kisspeptin is a multifunctional peptide (Prague and Dhillo, 2015), more extensive results are required to understand the complex pathways regulated by this peptide and the way these pathways are combined within the entire human body system by considering the various functional roles it plays. …”

The Changes of Serum Leptin and Kisspeptin Levels in Chinese Children and Adolescents in Different Pubertal Stages

“…Activating mutation of Kiss1 or Kiss1R gene can cause central precocious puberty in humans [9, 10]. Secondly, kisspeptin administration may accelerate vaginal opening (an external sign of puberty onset) in rodents and induces gonadotropins secretion and ovulation in both rodents and humans [11–13]. Thirdly, energy deficiency reduces hypothalamic kisspeptin expression and increases Kiss1 mRNA in adipose tissue in rodents [14].…”

Real-Time GnRH Gene Transcription in GnRH Promoter-Driven Luciferase-Expressing Transgenic Mice: Effect of Kisspeptin

“…Kisspeptin is involved in a variety of physiological developmental processes in the mammalian reproductive system [17,18]. Considering the potent stimulatory effect of kisspeptin on the electrical activity of GnRH neurons [19] and GnRH promoter activity [20,21], we hypothesized that kisspeptin may play a crucial direct role in regulating the GnRH pulse generator (presumably the origin of GnRH pulsatility), in the context of the hypothalamic neural network.…”