Infertility affects up to one in six couples in the United Kingdom (Human Fertilisation and Embryology Authority 2009, http://www.hfea.gov.uk/infertility-facts.html#1248). The currently available hormone-based treatments for inferti- lity act through the manipulation of the hypothalamic– pituitary–gonadal (HPG) axis at the level of GnRH or below. Although effective, these treatments also have a significant failure rate as well as an associated morbidity. The discovery of kisspeptin in 1996 and the subsequent identification of the kisspeptin receptor (previously known as G-protein-coupled receptor 54, GPR54) have added a new critical dimension to our understanding of the physiology of the HPG axis, reproduction and fertility (Lee et al. 1996, Clements et al. 2001). Mice and humans lacking kisspeptin receptor expression show a phenotype of hypogonadotrophic hypogonadism and conse- quent infertility (de Roux et al. 2003, Seminara et al. 2003). However, kisspeptin receptor knockout mice have normal levels of hypothalamic GnRH expression (Seminara et al. 2003) and normal GnRH neuronal morphology (Messager et al. 2005). These findings have been pivotal in the emergence of kisspeptin signalling as critical regulator of normal fertility, and future work may lead to the development of therapeutic use of kisspeptin in the treatment of reproductive disorders.
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