Since its first description in 1996, the KISS1 gene and its peptide products, kisspeptins, have increasingly become recognised as key regulators of reproductive health. With kisspeptins acting as ligands for the kisspeptin receptor KISS1R (previously known as GPR54 or KPR54), recent work has consistently shown that administration of kisspeptin across a variety of species stimulates gonadotrophin release through influencing gonadotrophin-releasing hormone secretion. Evidence from both animal and human studies supports the finding that kisspeptins are crucial for ensuring healthy development, with knockout animal models, as well as proband genetic testing in human patients affected by abnormal pubertal development, corroborating the notion that a functional kisspeptin receptor is required for appropriate gonadotrophin secretion. Given the large body of evidence that exists surrounding the influence of kisspeptin in a variety of settings, this review summarises our physiological understanding of the role of these important peptides and their receptors, before proceeding to describe the varying role they play across the reproductive lifespan.
Sophie A Clarke and Waljit S Dhillo
Saira Hameed, Channa N Jayasena and Waljit S Dhillo
The kisspeptins are a family of peptide hormones, which in recent years have been shown to play a critical role in the regulation of the hypothalamic–pituitary–gonadal axis, thus in turn influencing fertility and reproduction. This review examines the physiological role of kisspeptin and the kisspeptin receptor in the control of gonadotrophin and gonadal steroid hormone secretion and the implications of these findings with respect to fertility. In addition, the potential therapeutic use of kisspeptin in the treatment of reproductive disorders will be examined.
Waljit S Dhillo, Kevin G Murphy and Steve Bloom
The next 60 years promise to arouse the interest of scientists and clinicians while challenging the central dogmas of endocrine physiology. In this review we consider the fundamental changes in the understanding of endocrine physiology that have taken place in recent years and the new hormones discovered. We discuss how the brain is emerging as an important regulator of endocrine and neuroendocrine circuits. Advances in molecular biology techniques and the use of genomics and other -omics in furthering our understanding of endocrine physiology are also discussed. Finally, we propose that in 2066 we may prescribe designer hormones to healthy subjects.
Edouard G A Mills, Waljit S Dhillo and Alexander N Comninos
Reproduction is fundamental for the survival of all species and requires meticulous synchronisation of a diverse complement of neural, endocrine and related behaviours. The reproductive hormone kisspeptin (encoded by the KISS1/Kiss1 gene) is now a well-established orchestrator of reproductive hormones, acting upstream of gonadotrophin-releasing hormone (GnRH) at the apex of the hypothalamic–pituitary–gonadal (HPG) reproductive axis. Beyond the hypothalamus, kisspeptin is also expressed in limbic and paralimbic brain regions, which are areas of the neurobiological network implicated in sexual and emotional behaviours. We are now forming a more comprehensive appreciation of extra-hypothalamic kisspeptin signalling and the complex role of kisspeptin as an upstream mediator of reproductive behaviours, including olfactory-driven partner preference, copulatory behaviour, audition, mood and emotion. An increasing body of research from zebrafish to humans has implicated kisspeptin in the integration of reproductive hormones with an overall positive influence on these reproductive behaviours. In this review, we critically appraise the current literature regarding kisspeptin and its control of reproductive behaviour. Collectively, these data significantly enhance our understanding of the integration of reproductive hormones and behaviour and provide the foundation for kisspeptin-based therapies to treat related disorders of body and mind.