Neuroendocrine Role of Kisspeptin-Neurokinin B-Dynorphin Pathway in Male Fertility and its Correlation with Melatonin

Introduction: A subset of neurons has been recently identified in the arcuate nucleus of the hypothalamus that co-localize three neuropeptides; kisspeptin, neurokinin B, and dynorphin (KNDy). These neuropeptides have been shown to play a critical role in the central control of reproduction and the modulation of gonadotrophin releasing hormone (GnRH) secretion by endocrine, metabolic and environmental inputs. KNDy also acts as a novel potential therapeutic target in the treatment of fertility disorders. Infertility following chemotherapy is particularly common in male survivors of childhood cancer and for testicular cancer survivors. Early human studies have suggested that peripheral exogenous Kisspeptin administration stimulates GnRH secretion in healthy adults and in patients with some forms of infertility. In this review, we describe our current understanding of the neural systems mediating the actions of KNDy neurons on GnRH pulse generation and male fertility. In addition, the effect of melatonin treatment on the GnRH neuronal system and its effect on kisspeptin and gonadotropin-inhibitory neurons are discussed. Conclusion: Further researches about functional and molecular mechanisms of KNDy pathway, endogenous opioid peptide, and antioxidant agents, such as melatonin, may develop novel approaches to treat chemotherapy induced-infertility in males.