Hypothalamic neurokinin signalling and its application in reproductive medicine

The discovery of the essential requirement for kisspeptin and subsequently neurokinin B signalling for human reproductive function has sparked renewed interest in the neuroendocrinology of reproduction. A key discovery has been a population of cells co-expressing both these neuropeptides and dynorphin in the hypothalamus, directly regulating gonadotropin hormone releasing hormone (GnRH) secretion and thus pituitary secretion of gonadotropins. These neurons also project to the vasomotor centre, and their overactivity in estrogen deficiency results in the common and debilitating hot flushes of the menopause. Several antagonists to the neurokinin 3 receptor, forwhich neurokinin B is the endogenous ligand, have been developed, and are entering clinical studies in human reproductive function and clinical trials. Even single doses can elicit marked declines in testosterone levels in men, and their use has elicited evidence of the regulation of ovarian follicle growth in women. The most advanced indication is the treatment of menopausal vasomotor symptoms, where these drugs show remarkable results in both the degree and speed of symptom control. A range of other reproductive indications are starting to be explored, notably in polycystic ovary syndrome, the most common endocrinopathy in women. (C) 2021 Elsevier Inc. All rights reserved.

Automated summary

The essential requirement for kisspeptin and neurokinin B signalling in human reproductive function has sparked interest in the neuroendocrinology of reproduction. The discovery of neurons co-expressing these neuropeptides and regulating hormone secretion provides insight into reproductive processes and symptoms like hot flushes. Antagonists to the neurokinin 3 receptor show promising results in clinical studies for menopausal symptoms and may have potential in other reproductive indications.