Neurokinin B administration induces hot flushes in women.

Neurokinin B (NKB) is a hypothalamic neuropeptide binding preferentially to the neurokinin 3 receptor. Expression of the gene encoding NKB is elevated in postmenopausal women. Furthermore, rodent studies suggest that NKB signalling may mediate menopausal hot flushes. However, the effects of NKB administration on hot flushes have not been investigated in humans. To address this, we performed a randomised, double-blinded, placebo-controlled, 2-way cross-over study. Ten healthy women were admitted to a temperature and humidity-controlled research unit. Participants received 30 minute intravenous infusions of NKB and vehicle in random order. Symptoms, heart rate, blood pressure, sweating and skin temperature were compared between NKB and vehicle in a double-blinded manner. Eight of ten participants experienced flushing during NKB infusion with none experiencing flushing during vehicle infusion (P = 0.0007). Significant elevations in heart rate (P = 0.0106 vs. pre-symptoms), and skin temperature measured using skin probe (P = 0.0258 vs. pre-symptoms) and thermal imaging (P = 0.0491 vs. pre-symptoms) characteristic of menopausal flushing were observed during hot flush episodes. Our findings provide evidence that NKB administration can cause hot flushes in women. Further studies are required to determine if pharmacological blockade of NKB signalling could inhibit hot flushes during the menopause and during treatment for sex-steroid dependent cancers.

Evaluating the potential utility of kisspeptin to treat reproductive disorders.

The kisspeptins, encoded by the KISS1 gene, are a group of newly discovered peptides, which have been found to play an important regulatory role in human reproduction. Loss of function mutations of kisspeptin or the kisspeptin receptor have been shown to cause pubertal failure; whereas activating mutations cause precocious puberty. Central and peripheral administration of kisspeptin to mammals stimulates gonadotrophin secretion via gonadotrophin releasing hormone (GnRH) stimulation. Similar observations have been reported in human studies as well as an increase in luteinizing hormone (LH) pulsatility. Kisspeptin is now known to be associated with brain sexual differentiation, sexual dimorphism, pubertal initiation and sex steroids feedback loops, which will be discussed in this review. Metabolic state, stress, and other neuropeptides such as neurokinin B (NKB) are associated with changes in kisspeptin's stimulatory action. The conclusions from kisspeptin studies so far have led to the consideration of potential therapeutic applications, which will be discussed. Increasing our understanding of kisspeptin may aid our knowledge and management of infertility, contraception and hormone sensitive conditions.