New frontiers in kisspeptin/GPR54 physiology as fundamental gatekeepers of reproductive function

Front Neuroendocrinol. 2008 Jan;29(1):48-69. doi: 10.1016/j.yfrne.2007.07.002. Epub 2007 Aug 11.


Identification, in late 2003, of inactivating mutations of the G protein-coupled receptor GPR54 as causative factor for absence of puberty and hypogonadotropic hypogonadism in humans and mice was a major breakthrough in modern Neuroendocrinology, and drew considerable interest on the characterization of the roles of this receptor and its ligands (kisspeptins, encoded by the KiSS-1 gene) in the physiological control of essential facets of reproduction. After 3 years of intense research activity, kisspeptins are universally recognized as essential activators of the gonadotropic axis, with key roles in puberty onset and the control of gonadotropin secretion. While these fundamental functions are now well settled, novel aspects of kisspeptin/GPR54 physiology have emerged, including their involvement in the neuroendocrine control of ovulation and the metabolic gating of reproductive function. In addition, the 'comparative endocrinology' of this system has begun to be explored recently. These facets of kisspeptin/GPR54 function, as fundamental gatekeepers of reproduction, will be comprehensively reviewed herein.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Gonads / physiology
  • Humans
  • Hypothalamo-Hypophyseal System / physiology
  • Kisspeptins
  • Metabolic Networks and Pathways / genetics
  • Metabolic Networks and Pathways / physiology
  • Models, Biological
  • Ovulation / genetics
  • Ovulation / physiology
  • Puberty / genetics
  • Puberty / physiology
  • Receptors, G-Protein-Coupled / genetics
  • Receptors, G-Protein-Coupled / physiology*
  • Receptors, Kisspeptin-1
  • Reproduction / genetics
  • Reproduction / physiology*
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / physiology*


  • KISS1 protein, human
  • KISS1R protein, human
  • Kisspeptins
  • Receptors, G-Protein-Coupled
  • Receptors, Kisspeptin-1
  • Tumor Suppressor Proteins