The KiSS-1 receptor GPR54 is essential for the development of the murine reproductive system

Biochem Biophys Res Commun. 2003 Dec 26;312(4):1357-63. doi: 10.1016/j.bbrc.2003.11.066.


GPR54 is a G-protein-coupled receptor that displays a high percentage of identity in the transmembrane domains with the galanin receptors. The ligand for GPR54 has been identified as a peptide derived from the KiSS-1 gene. KiSS-1 has been shown to have anti-metastatic effects, suggesting that KiSS-1 or its receptor represents a potential therapeutic target. To further our understanding of the physiological function of this receptor, we have generated a mutant mouse line with a targeted disruption of the GPR54 receptor (GPR54 -/-). The analysis of the GPR54 mutant mice revealed developmental abnormalities of both male and female genitalia and histopathological changes in tissues which normally contain sexually dimorphic features. These data suggest a role for GPR54/KiSS-1 in normal sexual development, and indicate that study of the GPR54 mutant mice may provide valuable insights into human reproductive syndromes.

MeSH terms

  • Animals
  • Female
  • Genitalia / cytology*
  • Genitalia / embryology
  • Genitalia / physiology*
  • Hypogonadism / pathology
  • Hypogonadism / physiopathology
  • Kisspeptins
  • Male
  • Mice
  • Mice, Knockout
  • Mutation
  • Organ Specificity
  • Phenotype
  • Proteins / metabolism*
  • Receptors, G-Protein-Coupled
  • Receptors, Kisspeptin-1
  • Receptors, Neuropeptide / deficiency
  • Receptors, Neuropeptide / metabolism*
  • Reproduction / physiology*
  • Sexual Maturation / physiology*
  • Tissue Distribution


  • Kiss1 protein, mouse
  • Kiss1r protein, mouse
  • Kisspeptins
  • Proteins
  • Receptors, G-Protein-Coupled
  • Receptors, Kisspeptin-1
  • Receptors, Neuropeptide